# The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread



## nuke

This is a thread for topics which are not substantial enough to require their own threads due to their nature.

Please ask questions and ADD regulars will try to answer.


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## Rectify

*acronyms!*

what's a TRI?  somekind of reuptake inhibitor?


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## nuke

A triple reuptake inhibitor or SNDRI.


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## Rectify

ah, thanks.


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## poor milk

What is the difference between bk(MDMA) and MDMA? 

What does the the Beta ketone do? Does it disassociate when the drug gets metabolized?


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## nuke

The beta-keto refers to the ketone carbonyl group on the beta carbon (alpha carbon is the one connected to the nitrogen).

The ketone allows the drug around some laws and also makes the drug a little less lipophilic and gives it a different receptor binding profile compared to MBDB.

The oxygen ketone group (oxygen with a double bond to a carbon that is bonded to two other carbons) does not dissociate but is likely metabolized to an alcohol in the body.


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## Sturnam

What exactly does the "nor" prefix mean? Is it simply a dealkylated version of the original? Does it mean that it always comes off of the amine group?


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## seep

Is it possible to synthetize ω-conotoxin in such a way that it is effective IV, IM or PO? If so, how? If not, why not?


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## negrogesic

Without residue; NOR is short for "nitrogen one rest", German for "no residue at the nitrogen" (or something to that effect, spelling may be off). 

Often times its an alkyl functional group...


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## mad_scientist

^^^

True but the term is used more loosely now and doesn't always refer to nitrogen (e.g. noribogaine is the O-demethylated derivative). Usually for when a methyl group has been removed, but may be used more generally. 

As for ω-conotoxin, it won't be orally active as its a polypeptide and will be broken down by stomach acid, peptidase enzymes etc. It probably is active IM or IV but I imagine administering it peripherally will produce really nasty side effects, and only by selective central administration through intrathecal route can these be minimised and the central analgesic effects maximised. Or it just has really poor blood-brain barrier penetration and so won't get into the brain at all unless injected spinally.


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## TheLastAxon

Do the cathinone series, such as bk-mdma and bk-mbdb assert  their psychological effects primarily from uptake inhibition rather than monoamine release?


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## seep

mad_scientist said:


> As for ω-conotoxin, it won't be orally active as its a polypeptide and will be broken down by stomach acid, peptidase enzymes etc. It probably is active IM or IV but I imagine administering it peripherally will produce really nasty side effects, and only by selective central administration through intrathecal route can these be minimised and the central analgesic effects maximised. Or it just has really poor blood-brain barrier penetration and so won't get into the brain at all unless injected spinally.



It won't cross the BBB as mere ziconotide, but would it glide right through the BBB if enclosed in a liposome? Then there's still the challenge of getting it to not affect the PNS.


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## Too many doses

Why is tryptamine alone not a psychedelic?


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## negrogesic

TheLastAxon said:


> Do the cathinone series, such as bk-mdma and bk-mbdb assert  their psychological effects primarily from uptake inhibition rather than monoamine release?



Cathinones can also be release agents...


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## Hammilton

Too many doses said:


> Why is tryptamine alone not a psychedelic?



It's metabolised by MAO very rapidly, for one.  For two, I don't believe it has enough (any?) 5HT2a affinity.  I'm having trouble finding a paper that would even address this.

Interestingly, though, is evidence for tryptamine receptors (not serotonin receptors) in the brain.

J Pharmacol Exp Ther. 1985 Apr;233(1):75-9.
Related Articles, Links
    Click here to read
    Relationship between serotonin and tryptamine receptors in the rat stomach fundus.

    Cohen ML, Wittenauer LA.

    Tryptamine and serotonin (5-HT) are relatively potent contractile agonists in the rat fundus, a tissue in which contraction to 5-HT is not mediated by interaction with 5-HT1 or 5-HT2 receptors. The identification of [3H]tryptamine binding sites in the brain and fundus that show high affinity for certain beta-carbolines raised the possibility that 5-HT and tryptamine may be interacting with a similar receptor that is best described as a tryptaminergic receptor in the fundus. The affinity of five 5-HT receptor antagonists, ketanserin, metergoline, 1-(1-naphthyl)piperazine, LY154930 and LY175041 was similar when 5-HT or tryptamine was the agonist, indicating that 5-HT and tryptamine are interacting with the same receptor in the fundus. Furthermore, maximum contractile response to both 5-HT and tryptamine was reduced to the same extent by the calcium channel blocker, diltiazem, and by the calmodulin inhibitor, trifluoperazine. Inasmuch as diltiazem and trifluoperazine did not similarly inhibit contraction to agents interacting with other receptors (i.e., carbamylcholine), these data are consistent with the contention that 5-HT and tryptamine are interacting with the same receptor in the fundus. Consistent with this conclusion is the observation that affinity of the beta-carbolines, harmaline and harmine was also similar when tryptamine or 5-HT was used as the agonist. However, affinity of the beta-carbolines for the tryptamine/5-HT receptor in the fundus was dramatically lower than reported for [3H]tryptamine binding sites in brain membranes.(ABSTRACT TRUNCATED AT 250 WORDS)


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## shibireru

What are some readily obtainable substances which can produce death quickly, painlessly, and reliably?

Difficulty: No helium, carbon monoxide, nitrogen, nitrous oxide, or other inert gas.  

P.S.  I recently discovered that the handgun that I was planning to use if ever my hope should be exhausted was locked up.  The cathartic feeling of safety and control that it produced to know that I could use that gun to kill myself is now gone and I'm feeling claustrophobic.  I don't plan on killing myself right now, I just want these feelings of fear and worry over what travails the future has in store for me to abate; there's nothing worse than being trapped / cornered / helpless / stuck between a rock and a hard place.


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## nuke

I'm pretty sure questions about how to better kill yourself aren't allowed by the BLUA.


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## Too many doses

Thanks hammilton .


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## hugo24

Tryptamine appears to be somewhat active,read the reference in TIHKAL!

http://www.erowid.org/library/books_online/tihkal/tihkal53.shtml


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## shibireru

nuke said:


> I'm pretty sure questions about how to better kill yourself aren't allowed by the BLUA.



Isn't such advice subsumed under "harm reduction"?  Because a person intent on killing himself will try, regardless of how good or bad his methods are.  If a person goes about it in the wrong way, he may simply end up paralyzed or brain-damaged or something.  By providing this information, you'd be reducing the likelihood of such eventualities, and I needn't tell you that that is a good thing.

Moreover, from a moral perspective, to force a person to live (either actively or passively by omitting to provide information that could be used to end one's life) who wished to die is to do no better than to force someone to die who wished to live (i.e. murder).

If this is about warranting the site owners and members against legal trouble, then fine, but if this policy's purpose is to uphold morality, then I see no issue here.

And, as I say, this is more about creating a feeling of comfort and control for me than it is about actually killing myself.  I still have a number of options I am considering and only when/if those options are exhausted fruitlessly will I begin to more seriously contemplate suicide.  When the time comes for me to kill myself, I'll do it at all costs, so you may as well grant my request: better that I make use of a lower-risk method of suicide than higher-risk.

/I'm truly very sorry to steer the topic of conversation to my personal problems yet again, but this site is really one of the very few places I have to turn to.  I can't afford professional help anymore, and even if I could it would be pointless; I have tried 8 or more psychiatrists and psychopharmacologists in the past, each of whom has made things worse for me either by prescribing something that made me feel worse or by refusing to prescribe what I wanted whilst failing to refuse to take payment (which in my mind is fair if you're, you know, not actually providing a service).


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## nuke

If the end result is death, I fail to see how helping someone do it 'better' is harm reduction.

I mean, by the same logic, you could say that you're planning to murder a bunch of people and ask for the way that is the quickest and least painful and consider it harm reduction.


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## dorothyperkins

Of course it is! Death is, perhaps, the most harmful thing that can happen to somebody, but it is still possible to reduce the harm caused by it.  And couldn't euthanasia be considered harm reduction?


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## nuke

Not according to the BLUA.


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## Sturnam

Going back to the tryptamine question, I noticed that Shulgin said this later on in the tryptamine entry about tryptophan:



> Tryptophan, a natural and nutritionally essential amino-acid, is a centrally active intoxicant and sleep-provider in man. It is converted metabolically to tryptamine which is a little bit psychedelic. When administered with methionine (another amino-acid known to methylate things) it produces methylated tryptamines, the two best studied being N-methyltryptamine (NMT) and N,N-dimethyltryptamine (DMT).



Is he saying that tryptophan + methionine = methylated tryptamines _in vivo_? Does anyone know if there is any scientific articles about this, or if he's just guessing, or extrapolating from _in vitro_? 

This also seems to contradict what he says just before it:


> (with 15 g, orally, with 150 mg iproniazid) "This was a daily treatment given to schizophrenic patients, tryptophan along with an antidepressant which is a monoamine oxidase inhibitor. Most showed marked changes such as an elevation in mood, an increased involvement with other people in their ward, and an increased extrovertism. *A separate study of this combination with the addition of the amino acid l-methionine produced in about half of these patients a toxic or delirioid state*."



Anyone have more information about this?


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## shibireru

nuke said:


> Not according to the BLUA.



Sorry.  It's just that... where else is one to go to obtain this information?  The only forum on the internet that I can think of that allows this sort of discussion is alt.suicide.methods, but those people know next to nothing about pharmacology.  Besides that, because they are all very depressed - notwithstanding the numerous trolls - they are phlegmatic and perfunctory participators; even if they actually had some valuable information to share, it'd be pretty hard to provoke the conative portion of their psyches into activity of such a degree that they'd feel any compulsion at all to toss their hands lackadaisically at the keyboard until some travesty of what they had intended to type appeared on the screen.

tl;dr:  I must turn to people with a good understanding of pharmacology who have enough energy to respond to my question.  In my mind, that means bluelighters.  I can think of no other more appropriate place for this question.  Curse you, BLUA!


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## Hammilton

Right, because anyone would be stupid enough to engage in this activity.  There's a nurse not far from me facing extradition to Canada for supplying this sort of information to a girl who went through with it.

It seems that lately there have been more and more absurd attempts to twist "harm reduction" into some unrecognizable abomination to justify what the poster wants.  It's about reducing the damage caused by recreational drug use.   Suicide definitely doesn't fall under this.


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## shibireru

Hammilton said:


> Right, because anyone would be stupid enough to engage in this activity.  There's a nurse not far from me facing extradition to Canada for supplying this sort of information to a girl who went through with it.



Well, I didn't have it in mind that my question would be answered in this thread.  It takes all of one minute to create a new e-mail account and even less time to erase one.


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## Hammilton

You think anyone would risk jail time to help you kill yourself?

And I thought I had a big ego.


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## shibireru

Hammilton said:


> You think anyone would risk jail time to help you kill yourself?



No.  It's precisely because I deemed the risk of anything like that happening to be low that I am asking this question now - so low that it's negligible.  I would hate for anyone to risk imprisonment for my sake.

I mean, it's not as if I were going to write in my suicide note "I was talking to some people on the intarwebs and they told me how to go about ending my life!  They're screen names are: [...]"  I mean, how exactly would it be discovered that someone had given me advice - especially if that advice were transmitted in a surreptitious way, there being no vestiges of that correspondence whatever?  More problematic still: even if it could be proven that I had acted on advice given to me by some individual or another, it would be far more difficult to show beyond a reasonable doubt who that individual was, since most people have dynamic IP addresses that change with some regularity and because most people have wireless internet these days, so it can never be known for certain just who's leaching their connection.  Moreover, any advice I might receive would be acted upon months or years from now and I doubt any of the police officers or medical personnel investigating my death would think to ask themselves "Gee, might someone have helped him with this and if so who might that be?  I know, I'll scour every inch of the web in hopes of answering that question!"  (Even getting in touch with my ISP to find out which websites I had been visiting would do nothing.)

Besides I'm am not really sure that that constitutes, according the the law, assistance with suicide.  The fact that someone should have answered the question "What readily obtainable substances can produce death reliably, painlessly, and quickly?" wouldn't be proof of intent to abet a suicide.  It could be argued that the answering of the question was merely an intellectual exercise.

So what I am trying to understand is this: if both parties communicated through e-mail via newly registered e-mail addresses (and registered with false information at that), and those e-mail addresses were deleted immediately after the informational transaction had taken place and the suiciding party made it appear that he had obtained the information necessary to kill himself through his own research, how could the risk of imprisonment for whichever compassionate person had come to his assistance be greater than, say, .0000001%?


Whatever, I'll just learn how to crack my dad's safe...  I fucking hate this country and its demented theocratic laws.


Edit:  Look at ASHers or the busstop people (or whatever), for example: they are indirectly responsible, I'm sure, for dozens and dozens of deaths, yet none of them was ever arrested.  One of them had that website going for years on end containing advice on how to kill oneself and what implements to use and she was never indicted of any crime at all.  In many cases the idiot suicides had left clues as to where they'd gotten their information, leading the authorities right to that website, and although the address of residence and name of the proprietor could have been obtained within seconds, she never faced any legal troubles at all, not even so much as a civil suit, as far as I know.  I just don't think it bears even a fraction of a fraction of the risk which you say.  I would guess that there's just a little to your story about that Canadian nurse that you conveniently left out.


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## johanneschimpo

shibireru said:


> /I'm truly very sorry to steer the topic of conversation to my personal problems yet again, but this site is really one of the very few places I have to turn to. I can't afford professional help anymore, and even if I could it would be pointless; I have tried 8 or more psychiatrists and psychopharmacologists in the past, each of whom has made things worse for me either by prescribing something that made me feel worse or by refusing to prescribe what I wanted whilst failing to refuse to take payment (which in my mind is fair if you're, you know, not actually providing a service).



Did you know there is an entire sub-forum on bluelight, full of caring people who will talk to you and help you through your problems? 
Pills aren't always the best way to go. Maybe you could just use someone to talk to.

The Dark Side: http://www.bluelight.ru/vb/forumdisplay.php?forumid=47


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## nuke

Shibireru, your discussion is spiraling into irrelevance to this forum.  Further posts about it will be deleted.


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## any major dude

Why are halogens rarely seen in tryptamines, synthetic or otherwise?  I've heard of an aquatic source of 5-bromo-dmt, but nothing else... There seem to be so many in phenethylamines, it seems like someone would've tried it... I'd always thought this to be a bit strange... any thoughts?


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## Tsukasa

I completely agree with you shibiberu, but you're deviating this thread a bit. Though It seems to be a common problem with official or "large and nifty" threads.


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## Enkidu

Are positive allosteric modulators of the CB1 receptor recreational?


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## MurphyClox

@Enkidu:
Although I don't have evidence at hand for it, I would think: No, not really. At least not alone, i.e. without exogenic cannabinoids. The stimulation by endocannabinoids lasts normally only a very short time, due to fast _in vivo_ metabolism. Or not?

- Murphy


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## Tsukasa

^ what about FAAH inhibitors?


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## Hammilton

I have little experience with these, but it seems more likely that they'll produce antidepressant and anxiolytic effects (or maybe not the latter? not a common cannabinoid effect) but probably won't result in cannabimimetic-type effects, basically the way RIMA's don't produce MDMA or even Fenfluramine type effects.


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## Enkidu

Well, RIMAs aren't exactly GPCRs. I think a better correlation would be the action of benzodiazepines, which are (positive ?) modulators of the GABAa receptors. Yeah, I know, those aren't GPCRs either... but it seems to be a better correlation, at least to this poor guy.


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## Hammilton

What does receptor type matter?  FAAH inhibitors prevent / slow the metabolism of the relevant endocannabinoids, increasing EC concentrations.  RIMAs inhibit the metabolism of 5HT and NE, resulting in higher concentrations.

I don't think benzodiazepines are relevant at all.


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## Enkidu

Oh, wait. I see that you're responding to


> ^ what about FAAH inhibitors?


instead of me when you said:


> it seems more likely that they'll produce antidepressant and anxiolytic effects


I thought you meant 'they' to be CB1 modulators.

Why don't you think benzodiazepines are relevent?


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## Hammilton

Because they bind to and directly effect GABA-A receptors.  FAAH inhibitors slow the metabolism of the endogenous substances that bind to the CB1 and 2 receptors resulting in increased concentration.  RIMAs slow the metabolism of monoamines (5HT, NE, and to a lesser extent, DA), resulting in increased concentration.

Benzos have an activity that's entirely unrelated to these two; where FAAH inhibitors and RIMAs and MAOIs in general do basically the same thing with two different classes of drugs, benzos exert their effects directly on the receptor.  That's why they're not relevant here.


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## Enkidu

I'm still talking about positive modulation of the CB1 receptors. Benzodiazepines are somewhat more relevant to that discussion.


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## shibireru

Hammilton said:


> I have little experience with these, but it seems more likely that they'll produce antidepressant and anxiolytic effects (or maybe not the latter? not a common cannabinoid effect) but probably won't result in cannabimimetic-type effects, basically the way RIMA's don't produce MDMA or even Fenfluramine type effects.



Why is that anyways?  Simply because this sort of activity doesn't strongly conduce to disgorgement of neurotransmitters into the synapse?

I think you mentioned once that you had injected some endocannabinoids and said that they had had no noticeable effect.  This is even more interesting.  What reasonable hypothesis would account for this?  Is FAAH's catabolic activity comparable to MAO's?  Or does it have to do with the nature of the conformational change that endocannabinoids produce at the CB1 receptor?  That the pharmacodynamic activity of exocannabinoids like THC isn't well characterized yet and that they have affinities for other receptors as well?


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## Hammilton

Well, it's difficult to say, but it may be somewhat similar to that seen with monoamines, where just adding SE doesn't result in MDMA or psychedelic effects, adding DA doesn't result in amphetamine or cocaine like effects (though there is some very minimal evidence that l-dopa can be somewhat recreational, though we are talking pretty minimal, at least so far).



> Or does it have to do with the nature of the conformational change that endocannabinoids produce at the CB1 receptor?



I assume that it is related to this, though in animal models, they seem to produce changes somewhat related to that seen with exogenous cannabinoids.  Perhaps there are other endogenous cannabinoids that could do this, I'm not really sure.



> Is FAAH's catabolic activity comparable to MAO's?



I'd have to look into this more, but there are some pretty major differences between these.  It seems that all of the MAOIs are either irreversible (or they're reversible, but the concentrations required to reverse aren't clinically relevant for most part, though I'm sure that this is not entirely true, but seems to be for the most commonly used RIMAs, at least those I'm familiar with).  From what I know of FAAH inhibitors, they don't inhibit FAAH to nearly the extent that MAOIs do MAO.  It seems more comparable to other enzyme inhibitors like those used with opioid enhancement.

This might be entirely wrong, I've read very little on the subject and this is mostly the impression I've gotten.

But really, one trial isn't worth much and probably shouldn't be used for any sort of generalization.  There'll be people given fair doses of morphine who don't notice an effect either, and I tend to always expect nothing to happen with new new things.  All of this said, I have heard another report that had the same results (without the headache).

Ham



> I'm still talking about positive modulation of the CB1 receptors. Benzodiazepines are somewhat more relevant to that discussion.



Ah, I see.  I don't know.  I'm not even aware of any, honestly.


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## Sturnam

Well, since I think my question got lost in the suicide debate, here it is again.

This is the quote for TiHKAL tryptamine entry:


> Tryptophan, a natural and nutritionally essential amino-acid, is a centrally active intoxicant and sleep-provider in man. It is converted metabolically to tryptamine which is a little bit psychedelic. When administered with methionine (another amino-acid known to methylate things) it produces methylated tryptamines, the two best studied being N-methyltryptamine (NMT) and N,N-dimethyltryptamine (DMT).



Is he saying that tryptophan + methionine = methylated tryptamines _in vivo_? Does anyone know if there is any scientific articles about this, or if he's just guessing, or extrapolating from _in vitro_?


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## Hammilton

No idea, but I was much more interested in the "centrally active intoxicant" part.

Has there been any reports at erowid or bluelight of a recreational tryptophan overdose?


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## hamhurricane

*quick worm question?*

there was a study linked off "the dark side" which discussed an opioid containing silk worm, i found the journal article but i remember it saying the worms contained ß-endorphin and Leu-enkephalin, was i reading it right? there was nothing novel in the worms just two endogenous opioids?


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## MurphyClox

@Sturnam: Methionine alone is NOT a methylating agent. One needs rather S-adenosyl-methionine, which won't methylate anything without the help of the proper enzyme though. Looking at the biochemical significance of methionine, I doubt that the combo _Trp + Met_ will yield a significant amount of DMT resp. NMT in vivo. No chance!

- _Murphy_


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## TheLastAxon

Is it likely that Methylone could form into toxic metabolites that would result in reactive quinone species? I understand that it's lower SE/DA activity would mean an overall lower chance of toxicity, but I'm wondering about the potential for toxicity from methylone alone if combined with amphetamine.


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## mr.dopeman

*advanced THC and other cannabinoids solubility*

Does anyone know the solubility of THC and other cannibinoids in solvents such as ethanol, isopropyl alcohol, and acetone. And specifically at spefcific temepratures. Are Thc and any other of the cannibinoids insoluble in any of those solvents at a temeprature achivable in a freezer?


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## leungkachong

Hammilton said:


> Well, it's difficult to say, but it may be somewhat similar to that seen with monoamines, where just adding SE doesn't result in MDMA or psychedelic effects, adding DA doesn't result in amphetamine or cocaine like effects (though there is some very minimal evidence that l-dopa can be somewhat recreational, though we are talking pretty minimal, at least so far).



In the case of l-dopa... it appears that the mesolimbic effect is so weak that the brain essentially mistakes the discrepancy between expected reward and actual reward to another pleasurable stimulus, rather than the l-dopa itself.  I believe you were probably referring to dopamine dysregulation syndrome (or "why the l-dopa'd up parkinson's patient is using his limited motor capacity to hump your leg and gamble").

Actually, I even feel uncomfortable describing it in this manner.  Rip out the VTA or the Nuc.Acc.(well, pull out the Talairach atlas and perform some stereotactic surgery), and give our furry rodent friends an all access pass to some DA-ergic drugs... and they'll still go for them (ie - they still are re-inforcing, and therefore likely 'pleasurable').  What they WON'T do is get off their ass and perform a task to get the drugs.

That's evidence for at least a single dissociation between 'liking' and 'wanting'.  And any drug addict knows that they aren't always taking the drug cuz they 'like' it, they just want it.  The reward pathway is probably more accurately described as the 'desire pathway'.  And in that case, l-dopa does represent DAergic activity just as well as amphetamine (using one of your examples)... as it allows us to distinguish OUTSIDE cues as what we want, rather than the mutant-weirdo DA-wannabe amphetamine.

ps- I love talking about science like that, but I don't know if it makes it harder to understand... if it is, I'll go back to my boring formal descriptions.


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## blau1005

Not sure if this is the thread for it, but it doesn't deserve it's own thread. This may be better placed in the GFJ FAQ, but I'm looking for some specific 'ADD style' answers  If this isn't the spot please let me know where to ask this stuff.

Mr Blonde suggested that grapefruit juice may inhibit CYP2D6 as well as CYP3A4 and a bunch of other enzymes. He linked to this article. I don't have access to that service so can't read the full article but have a few questions about the abstract.

1. What does this mean: "All four furanocoumarins clearly inhibited CYP3A4-catalyzed nifedipine oxidation in concentration- and time-dependent manners, suggesting that these compounds are mechanism-based inhibitors of CYP3A4."

2. "Inhibitor concentration required for half-maximal rate of inactivation (KI) values for bergamottin, DHB, GF-I-1, and GF-I-4 were calculated, respectively, as 40.00, 5.56, 0.31, and 0.13 μM, whereas similar values were observed on their inactivation rate constant at infinite concentration of inhibitor (kinact, 0.05–0.08 min−1)."
What is the half-maximal rate of inactivation? Does this mean the enzyme's efficacy was reduced to half?

3. Any other information regarding furanocoumarins inhibiting CYP2D6? The feeling seems to be that GFJ potentiates codeine but not to any great extent.  I am wondering whether the CYP2D6 inhibition could be responsible for this; ie it inhibits CYP3A4 which increase efficacy of the codeine, but the inhibition of CYP2D6 means that this potentiating action is not felt as much. And yeah this could be due to users consuming GFJ with low levels of the furanocoumarins but even those using fresh juice don't report any great response. Also how does the ceiling effect come in to play here?

Cheers guys!


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## Sturnam

^^^ for #2:
yes. They're just giving the IC50. means that 50% of the enzyme is inihibited. it's just a standard unit of sciencey stuff.

and #3, GFJ does NOT potentiate codeine. it fact, it does the opposite. codeine is a prodrug that is metabolized to morphine through CYP2D6, so if you inhibit that, then you don't get any morphine.


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## Black

#1 essentially means that the data fits together. if you measure inhibition of enzymes that is not concentration dependent chances are you have fucked up or are measuring something different than you intended...
if the inhibition is proportional to the concentration of the supposed inhibitor you sort of know that the substance you tested is the one responsible.


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## ebola?

To return to the cathinone derivative question, does methylone cause primarily dopaminergic reuptake inhibition or release via transporter reversal?  I have heard conflicting reports...and should probably get off my ass and look up the journal article.

ebola


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## ebola?

Another question: I heard someone in here argue that some people experience attenuation of dopaminergic releasers' effects when on selegiline because selegiline itself interferes with DA transporter reversal.  By which mechanisms could this be possible?

ebola


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## Coolio

Maybe it's the l-meth and l-amph metabolites? The DA transporter reversal seen with amphetamine was with racemic right?


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## any major dude

Don't know if this deserves its own thread or not, but anyway... I know some isoquinolines have an inhibitory effect on acetylcholinesterase, and some may affect MAO A & B.  I can see how the latter would cause otherwise inactive alkaloids in various species of cacti to be active, but I haven't been able to find much info on which isoquinolines are in trichocereus cacti, or by which mechanism they may cause activity.  Anyone know much about this?  or know of a study or paper to direct me to?


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## Sturnam

*ebola?*

Found this article.



> Methcathinone, the benzylic ketone analog of methamphetamine (MA), and methylone, the benzylic ketone analog of 3,4-methylenedioxymethamphetamine (MDMA), were synthesized and tested for their abilities to inhibit monoamine uptake in vitro. Methcathinone and methylone were threefold less potent than MA or MDMA at inhibiting [3H]5-HT uptake into human platelets, with IC50's of 31.4 ± 7.3 uM and 5.8 ± 0.7 uM, respectively. In C6 glial cells stably expressing the rat dopamine transporter, methcathinone and methylone were similar in potency to MA and MDMA, with IC50's for [3H]DA uptake of 0.36 ± 0.06 uM and 0.82 ± 0.17 uM, respectively. Methcathinone and methylone were also similar in potency to MA and MDMA in C6 cells expressing the human norepinephrine transporter, with IC50's for [3H]NE accumulation of 0.51 ± 0.10 uM and 1.2 ± 0.1 uM, respectively. The benzylic ketone moiety of methcathinone and methylone had a large (tenfold) negative impact on the abilities of these drugs to inhibit the vesicular monoamine transporter (VMAT2) compared to MA and MDMA. In VMAT2-containing bovine chromaffin granules, the IC50's for [3H]5-HT uptake were 103 ± 15 uM for methcathinone and 125 ± 16 uM for methylone. *These results indicate that methcathinone and methylone are potent and selective inhibitors of plasma membrane catecholamine reuptake transporters*, with more modest effects at the serotonin reuptake transporter. These drugs are essentially inactive at the vesicular monoamine transporter.



From here:
NV Cozzi, MK Sievert, AT Shulgin, P Jacob III, AE Ruoho. Methcathinone and 2 methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (methylone) selectively inhibit plasma membrane catecholamine reuptake transporters. Soc. Neurosci. Abs., 24, 341.8 (1998)


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## blau1005

Sturnam said:


> GFJ does NOT potentiate codeine. it fact, it does the opposite. codeine is a prodrug that is metabolized to morphine through CYP2D6, so if you inhibit that, then you don't get any morphine.



Thanks for the answers. This is kind of what I was getting at. GFJ does inhibit CYP3A4, increasing the efficacy of the morphine (that comes from the codeine). However because CYP2D6 is also inhibited, does this mean that GJF has zero net effect on the drug's action? Or does it inhibit CYP2D6 less than CYP3A4, meaning that using GFJ would overall add to the effects?

Cheers


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## Sturnam

Well, some of the flavinoids described mainly inhibit CYP3A4, and some mainly inhibit CYD2D6. I guess it would depend on the ratio of these flavinoids in the grapefruit, as well as how active your CYP2D6 enzymes are in the first place.

Overall, I think that the CYP3A4 inhibition is greater, but the CYP2D6 inhibition basically the rate limiting step. So even if the morphine sticks around longer, the codeine will be processed much slower, and probably will decrease the subjective high. Also, because CYP2D6 is inhibited, it means that more of the codeine will take alternative metabolic pathways, which would result in other, weaker metabolites.


----------



## blau1005

Thanks. I get the feeling that GFJ might be worth a go once or twice, but those who have found success with it are outweighed by those who haven't. I guess there's only so much you can do with codeine.


----------



## johanneschimpo

why not use a (selective) CYP3A4 inhibitor?


----------



## acetylcholine

Quick question that I don't think requires a separate thread.

Psychedelics like LSD and Psilocin are 5-ht2a agonists. They also usually make people feel good, and are sometimes even abused by depressed people for their mood improving effects effects.

Atypical Antidepressants like Mirtazapine and Trazodone are 5-ht2a *antagonists*. They are prescribed to depressed people to improve mood and are sometimes quite effective.

What gives? I have some inkling that the answer has to do with 5-ht2a receptors being found in different parts of the brain and dopamine release, but I don't have a concrete answer.

Can someone explain this seemingly paradoxical situation?


----------



## Hammilton

It's pretty hard to find evidence regarding real abusive use of psychedelics.  They're pretty self limiting, both the physical and mental exhaustion that often results after their use, but even more so, the tachyphylaxis makes it rather impossible.  I've seen the occasional trip report documenting a depressed person using the drug to lighten their mood, but not anything that constitutes abuse.  It'd be interesting to know how often even this sort of use occurs, though.

Mirtrazepine and Trazodone both have activities that go far beyond 5HT2a antagonism, and these other activities are too relevant to ignore for the sake of discussion.  Are there any pure, selective 5HT2a antagonists that produce antidepressant-type effects?  I don't know of any off the top of my head.

Despite all of this, I don't think it's neccessary to go much into their actions to explain it.

Psychedelics have their name for a good reason, they "manifest the soul," so to speak.  They enable and sometimes force the user to think and address psychological issues and help to resolve them.  I think the antidepressant effect they produce can be entirely explained by the cognitive effects they produce.

Mirtrazepine and Trazodone's effects can be explained without even involving their direct action of 5HT2a.

Perhaps this is all wrong.  It's getting late and I'm getting tired; I don't feel like going through a bunch of journals right now.


----------



## shibireru

Hammilton said:


> Are there any pure, selective 5HT2a antagonists that produce antidepressant-type effects?  I don't know of any off the top of my head.



Ritanserin is, I believe, and appears to have anti-depressant properties.  Perhaps also eplivanserin, altanserin, setoperone, and etoperidone.  Probably not, but I am feeling much too lazy right now to track down information concerning their receptor affinities.


----------



## shibireru

acetylcholine said:


> Quick question that I don't think requires a separate thread.
> 
> Psychedelics like LSD and Psilocin are 5-ht2a agonists. They also usually make people feel good, and are sometimes even abused by depressed people for their mood improving effects effects.
> 
> Atypical Antidepressants like Mirtazapine and Trazodone are 5-ht2a *antagonists*. They are prescribed to depressed people to improve mood and are sometimes quite effective.
> 
> What gives? I have some inkling that the answer has to do with 5-ht2a receptors being found in different parts of the brain and dopamine release, but I don't have a concrete answer.
> 
> Can someone explain this seemingly paradoxical situation?



You should remember that all - or as far as I know anyway - serotonergic psychedelic hallucinogens can cause bad trips and severe anxiety - especially in those who are already feeling depressed and anxious.  Perhaps people enjoy themselves while on these drugs despite their capacity for dysphorigenesis (i.e. their basal level of happiness and the pleasure of being thrust into some strange new world are great enough to counteract the dysphoria-encoding neurotransmission that these substances engender.)

Ayuhnoh :shrugs:


----------



## blau1005

johanneschimpo said:


> why not use a (selective) CYP3A4 inhibitor?



Don't know of any that aren't Rx.


----------



## Enkidu

They are saying that the serotonin hypothesis of depression is BS. Apparently the advertisements/product pushing by drug companies marketing SSRIs have bolstered the hypothesis without enough corresponding scientific data.

For another paradoxical treatment option, look into tianeptine (a selective serotonin reuptake enhancer) vs. all the selective serotonin reuptake inhibitors.

It should be noted that the individual's body chemistry is also important. Slight, preexisting imbalances (i.e., the chemical reason that the individual is depressed, which varies from individual to individual) obviously play a role in dictating the proper therapy.


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## ebola?

acetylated choline? said:
			
		

> Psychedelics like LSD and Psilocin are 5-ht2a agonists. They also usually make people feel good, and are sometimes even abused by depressed people for their mood improving effects effects



Yet all of these recreational drugs are 'dirty' in various respects.  I cannot think of a pure(ish) 5ht2a agonist in common use.  What is more, IIRC, Nichols researched a highly potent 5ht2a agonist that did not yield psychedelic effects.  Things are getting weird and complicated, the more we discover (as always).



> Atypical Antidepressants like Mirtazapine and Trazodone are 5-ht2a antagonists. They are prescribed to depressed people to improve mood and are sometimes quite effective.



OFF-TOPIC mirtazapine digression:

mmm...mirtazapine (which I take for insomnia) is...perhaps the dirtiest drug evar.   I believe that the majority of anti-depressant effects may be attributed to antagonism at a2 adrenergic auto-receptors, which appears to cause increased release of 5ht and NE, in particular enhancing activity at 5ht1a (given the patterns of the drug's 5ht antagonisms).  I believe that sedation and anxiolysis may be attributed mainly to H1 agnoism (mostly sedative) and antagonism at 5ht2c (likely quite anxiolytic.  Remember that mCPP, a solid 5ht2c agonist, among other things, is commonly referred to as a 'panicogen'), maybe antagonism at 5ht2a, and maybe antagonism at 5ht3 (activity here means that mirtazapine doesn't cause the nausea and sexual side-effects that we see with SSRIs, but it also means that weight gain will be likely).

Weird drug.




			
				hammilton said:
			
		

> Psychedelics have their name for a good reason, they "manifest the soul," so to speak. They enable and sometimes force the user to think and address psychological issues and help to resolve them. I think the antidepressant effect they produce can be entirely explained by the cognitive effects they produce.



Seems parsimonious enough.



> They are saying that the serotonin hypothesis of depression is BS. Apparently the advertisements/product pushing by drug companies marketing SSRIs have bolstered the hypothesis without enough corresponding scientific data.
> 
> For another paradoxical treatment option, look into tianeptine (a selective serotonin reuptake enhancer) vs. all the selective serotonin reuptake inhibitors.
> 
> It should be noted that the individual's body chemistry is also important. Slight, preexisting imbalances (i.e., the chemical reason that the individual is depressed, which varies from individual to individual) obviously play a role in dictating the proper therapy.



I concur, with caveats.  Assuming that SSRIs are marginally effective rather than ineffective, given the time-course of their efficacy, there has to be some sort of downstream change in neuroanatomy and/or chemistry that exerts an anti-depressant effect.  Whether this is because they correct some prior 'imbalance' in neural circuits involving 5ht transmission is completely unclear.

ebola


----------



## acetylcholine

Shite... I wish I had started a new thread now. This seems to be generating a lot of really interesting discussion.  I guess it's too late now.

I want to mention several things in response to what people have said, but I have to run to work.

I do want to mention quickly, though, that at least some SSRI's also block 5-ht2a receptors as Mirtazapine does. Fluoxetine does this, which may explain why people on Prozac require higher doses of, or get very little effect from psychedelics.


----------



## Enkidu

ebola? said:


> I concur, with caveats.  Assuming that SSRIs are marginally effective rather than ineffective, given the time-course of their efficacy, there has to be some sort of downstream change in neuroanatomy and/or chemistry that exerts an anti-depressant effect.  Whether this is because they correct some prior 'imbalance' in neural circuits involving 5ht transmission is completely unclear.



There is an article called _Biological Markers of Depression_ that discusses this. (I have the whole book in front of me.  ) Yes, downstream changes do cause the persistent mood change, but that is still the result of a correction in a chemical 'imbalance.' There are a variety of chemical hypotheses of depression. So when I said,


> It should be noted that the individual's body chemistry is also important. Slight, preexisting imbalances (i.e., the chemical reason that the individual is depressed, which varies from individual to individual) obviously play a role in dictating the proper therapy.



I in no way meant to restrict 'chemical imbalance' to serotonin. It is even true that different chemical imbalances cause different types of depression!


----------



## Enkidu

ebola? said:


> Yet all of these recreational drugs are 'dirty' in various respects.  I cannot think of a pure(ish) 5ht2a agonist in common use.  What is more, IIRC, Nichols researched a highly potent 5ht2a agonist that did not yield psychedelic effects.  Things are getting weird and complicated, the more we discover (as always).



Oh, I forgot to ask, which one was this?


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## ebola?

Hah...I don't know enough to go further in this discussion without looking up journal articles (on which I'm pretty damned burnt, writing a research proposal right now).
...
Another fucking selegiline question:
what do people think of careful use of MDMA + selegiline?
I believe that Nuke posted a study recently suggesting that selegiline will combat neurotoxicity without outright toxic increases in hyptertension and hyperthermia.  

So in vivo, in humans, which moderating effect of selegiline will win out:
increased neurotoxicity from increased hypothermia or decreased neurotoxicity from reduced formation of peroxides from the action of MAOB.

Now, given the rife impurities in street ecstasy, I think that this question should remain strictly theoretical.  It would be nigh impossible to safely titrate up to a safe but active dose of MDMA that one could repeat when using 'wares' with unclear content and dosage.

ebola


----------



## Tsukasa

^ People shoudn't refer to "ecstacy pills" as MDMA. Theirs only a slight chance it's actually MDMA or even an analogue. It's like russian roullete. Unless you get high grade MD(X)A from a reliable chem vendor, then I wouldn't risk using selegiline with anything you think is molly.


----------



## leungkachong

ebola? said:


> Yet all of these recreational drugs are 'dirty' in various respects.  I cannot think of a pure(ish) 5ht2a agonist in common use.  What is more, IIRC, Nichols researched a highly potent 5ht2a agonist that did not yield psychedelic effects.  Things are getting weird and complicated, the more we discover (as always).



It appears that the differential activation of catalytic activity (or of the G protein subunits) is what underlies whether a 5-HT2A agonist is psychedelic or not.  Which also means that F&B's SAR can only bring us so far, as we don't yet understand the microdomain interactions which decide whether we get more/any PLC vs PLA2 activity.  Yah, it's the phospholipase C doing the PIP2 --> IP3 + DAG that seems to be necessary+sufficient.

I guess it'd be pretty damn cruel to constituitively activate the PLC-mediating subunit... but it's not weird and complicated, just selective/picky.  And this signal-directed trafficking stuff REALLY expands our repertoire and pharmacologists!


----------



## acetylcholine

shibireru said:


> Ritanserin is, I believe, and appears to have anti-depressant properties.  Perhaps also eplivanserin, altanserin, setoperone, and etoperidone.  Probably not, but I am feeling much too lazy right now to track down information concerning their receptor affinities.


Ritanserin and its analogues are pretty close. They have no affinity for Histamine receptors or a2 receptors like tetracyclic AD's, so someone who takes it should really be able to "feel" only the 5-HT effect. I say 5-HT and not 5-HT2a because, according to IUPHAR, it has affinity for just about every serotonin receptor as well as a1. Still, its effect is strongest on 5-HT2a, and if it is indeed a relatively efficacious antidepressant according to clinical studies, then there you go. 

Considering the fact that Yohimbine has undeniably imo, antidepressant effects, and it is a relatively selective a2 blocker, I would wager to say that a2 antagonism is likely a stronger, and certainly faster antidepressant route than 5-HT antagonism. However, from my experience, tetracyclics' a2 is effect is hardly noticeable compared to Yohimbine. I never stayed on a tetracyclic for long, but it never felt anything like Yohimbine, or any stimulant for that matter. Any Remeron users here care to differ?

According to this abstract posted on biopsychiatry.com:
http://biopsychiatry.com/schizoserotonin.htm


> In the prefrontal cortex, 5-HT(2A)-receptors stimulation increases the release of glutamate


Considering the evidence for NMDA antagonists as potential antidepressants, it seems reasonable to me say that 5-HT2a antagonists may work through this route. I say this because, if I remember correctly, Ketamine functions as an antidepressant by increasing glutamate receptor _subtype_ activation.

Your thoughts?


----------



## ebola?

> I never stayed on a tetracyclic for long, but it never felt anything like Yohimbine, or any stimulant for that matter. Any Remeron users here care to differ?



I'm yohimbine naive and plan to stay that way.
I have a working hypothesis that adrenergic activation in isolation of alternate 'euphorogenesis' feels fucking bad, man. 

ebola


----------



## acetylcholine

ebola? said:


> I'm yohimbine naive and plan to stay that way.
> I have a working hypothesis that adrenergic activation in isolation of alternate 'euphorogenesis' feels fucking bad, man.
> 
> ebola



Funny you say that. When I first tried _Yohimbe_, I fucking hated it too. I felt nauseous, feverish, and dizzy, a feeling akin to smoking too many cigarettes. I stayed away for years because of that bad experience. I now know that my bad experience was very likely due to my ingesting GNC Yohimbe bark extract, rather than pure alkaloid. There are many active chemicals in the bark other than Yohimbine and it's spatial isomers. Some of these impurities are possibly MAOIs, and I believe that is what made me feel sick.

Years later, I decided to try Yohimbine HCl, and I was surprised how effective of an atypical stimulant it was. There was no nausea or other nasty peripheral side effects at up to 7.5 mg. It is not euphoric, but there is a definite positive CNS effect. I find it's an effective appetite suppresant and all around mood brightener. It's also great for treating dry mouth due to medication. Yohimbine would never pass as a desirable illicit "drug," but it is a terrific nutritional "supplement."

Too much will cause side effects even without nausea; I get tremors, racing thoughts, and muscle stiffness from too much Yohimbine, but it's no big deal to me.


----------



## shibireru

acetylcholine said:


> Considering the fact that Yohimbine has undeniably imo, antidepressant effects, and it is a relatively selective a2 blocker, I would wager to say that a2 antagonism is likely a stronger, and certainly faster antidepressant route than 5-HT antagonism.



Yohimbine is a 5-HT1A, 5-HT1D, and 5-HT2A agonist and a 5-HT1B, 5-HT2B, and alpha 2 adrenergic receptor antagonist.

When I take yohimbine, I feel excruciatingly bored, aboulic, and anhedonic (or more so than usual anyways), but when it wears off, I feel quite blissful and sociable.  It seems to be that its anti-depressant effect lies within its rebound effects - at least for me.

The other day I conducted a little, fairly risky experiment wherein I took 50 micrograms of clonidine with 500 or 1000mg of Yohimbe bark powder every half an hour for two hours and threw in a few hundred milligrams of 5-hydroxytryptophan for good measure.  I felt better the next day than I had in years.  (5-HTP alone makes me feel worse, so it probably wasn't that.)


----------



## acetylcholine

> Yohimbine is a 5-HT1A, 5-HT1D, and 5-HT2A agonist and a 5-HT1B, 5-HT2B, and alpha 2 adrenergic receptor antagonist.
> 
> When I take yohimbine, I feel excruciatingly bored, aboulic, and anhedonic (or more so than usual anyways), but when it wears off, I feel quite blissful and sociable. It seems to be that its anti-depressant effect lies within its rebound effects - at least for me.
> 
> The other day I conducted a little, fairly risky experiment wherein I took 50 micrograms of clonidine with 500 or 1000mg of Yohimbe bark powder every half an hour for two hours and threw in a few hundred milligrams of 5-hydroxytryptophan for good measure. I felt better the next day than I had in years. (5-HTP alone makes me feel worse, so it probably wasn't that.)


The fact that Yohimbine HCl, and especially the sum of Yohimbe bark hits those 5-HT receptors does make it an imperfect tool for gauging a2 behavioral and cognitive response. That's why I'm in search of people who have experienced highly selective a2 antagonists in my other Yohimbine discussion here:
http://www.bluelight.ru/vb/showthread.php?t=433550

Anyway, it's funny that you attribute Yohimbe's 5-HT action to its antidepressant action. Reading your experiment, the first thing I would guess is that the rebound effect is due to the absence of Clonidine the next day, but that of course is not the case. I think both scenarios are possible in different individuals; I also find Cholinergics to have an antidepressant quality, while many people find anticholinergics -in moderation- to be euphoric.


----------



## Tsukasa

shibireru said:


> Yohimbine is a 5-HT1A, 5-HT1D, and 5-HT2A agonist and a 5-HT1B, 5-HT2B, and alpha 2 adrenergic receptor antagonist.
> 
> When I take yohimbine, I feel excruciatingly bored, aboulic, and anhedonic (or more so than usual anyways), but when it wears off, I feel quite blissful and sociable.  It seems to be that its anti-depressant effect lies within its rebound effects - at least for me.
> 
> The other day I conducted a little, fairly risky experiment wherein I took 50 micrograms of clonidine with 500 or 1000mg of Yohimbe bark powder every half an hour for two hours and threw in a few hundred milligrams of 5-hydroxytryptophan for good measure.  I felt better the next day than I had in years.  (5-HTP alone makes me feel worse, so it probably wasn't that.)



I think you have agonist and antagonist messed up. I thought it was the other way around. It antagonizes those 5-HT receptors, and increases activity or noradrenaline, dopamine, and nitric oxide.


----------



## shibireru

Tsukasa-

Well, it most certainly does increase synaptic noradrenaline levels, since it is an alpha 2 antagonist.  It is not, however - assuming that what I've read is correct (and it may very well be incorrect as you know) - a dopamine agonist, but rather an antagonist at certain dopamine receptors.  Which it antagonizes specifically I'm not sure.

I don't know anything about its effects on nitric oxide levels.


----------



## shibireru

acetylcholine said:


> Reading your experiment, the first thing I would guess is that the rebound effect is due to the absence of Clonidine the next day, but that of course is not the case. I think both scenarios are possible in different individuals; I also find Cholinergics to have an antidepressant quality, while many people find anticholinergics -in moderation- to be euphoric.



Yes, I utterly despise anything significantly noradrenergic or adrenergic.  On the other hand, I don't especially like adrenergic antagonists either (*).  My favorite substances are those which produce minimal effects of adrenergic/noradrenergic currents.


* Interesting story:  I almost died from a labetalol overdose last night.  I took a fairly typical dose after I had eaten, which is something I have never done before: evidently taking it on a full stomach vastly increases bioavailability.  I took it for the purpose of maintaining normal sypathetic tone in the face of large doses of phenylethylamine.  When I perceived various symptoms of overdose, including dyspnea, dizziness, bradycardia, and hyptension, I did everything I could to reverse this condition, taking significant quantities of amphetamine, salbutamol, and more phenylethylamine; but nothing worked!  My heart rate rose only to 60 bpm and I was still hypotensive.  To make matters much more frightening, my autonomic nervous system seemed to be gravely malfunctioning:  I realized that if ever I ceased to consciously focus on breathing, my breathing would stop.  At various points in the evening I would go 30 seconds or more without breathing and without experiencing any air hunger whatever.  So I had to stay up until the labetalol had mostly worn off.

Scary shit!  (Not dying but the thoughts of living as a vegetable)


----------



## acetylcholine

> evidently taking it on a full stomach vastly increases bioavailability


First of all, gald you're okay. Scary shit indeed, but informative. I sometimes function under the same impression that _all substances work more strongly on an empty stomach_. This is not always the case, apparently with catastrophic results.


> I did everything I could to reverse this condition, taking significant quantities of amphetamine, salbutamol, and more phenylethylamine


I know the feeling. I have, due to poor judgement, had times when I've ingested too much of an anticholinergic substance, either for the purpose of treating severe nausea or motion sickness, or long in the past as pure experimentation. The nasty anticholinergic syndrome would linger into the next day and I would try every cholinomimetic drug I had to reverse the condition: huperzine, donepezil, carnitine, indirect releasers of acetylcholine, nothing would help. It's as if those stubborn muscarinic receptor blockers refused to budge.


----------



## Tsukasa

shibireru said:


> Tsukasa-
> 
> Well, it most certainly does increase synaptic noradrenaline levels, since it is an alpha 2 antagonist.  It is not, however - assuming that what I've read is correct (and it may very well be incorrect as you know) - a dopamine agonist, but rather an antagonist at certain dopamine receptors.  Which it antagonizes specifically I'm not sure.
> 
> I don't know anything about its effects on nitric oxide levels.



I think i may have yohimbine mixed up with something else, or i've read incorrect information, sorry about that. Though reading up on it from a more reliable source, i see it's only a weak partial agonist at 5-HT1A, 5-HT1D, and 5-HT2A, not a full agonist.


----------



## Enkidu

Does BZP have any analgesic action?

PS: This topic should prolly be sticky'd.


----------



## dunwich

*to sound like an idiot or to not sound like an idiot...oh dern im already posting*

*Benzos/alprazolam + ethyl alcohol:*

Is there any reasonable explanation to why when I take a low-moderate benzo dose(1-2mg alprazolam) with or without tolerance an hour or so before I start drinking that by the end of the night I am not drunk? I do drink less, but not that much less - and not because i am getting wasted. Im just being cautious. Then if i try to get wasted and succeed i dont end up blackout status...just normal wasted. 

For me, it seems harder to feel the effects of alcohol when on benzos. The other night I had 1mg alprazolam before drinking and 2x redose at .5mg during alcohol consumption. I ended up drinking 5-7 16oz 5% etoh beers and then more than a few big swigs of wine. The people i was with were reasonably intoxicated, i was not. 

In previous experiences with alprazolam and alcohol as the day turns to night I end up thinking "Wtf...benzos seem to just block all the bad effects of alcohol and make my benzos work better."  It really feels like when i drink moderately on a reasonable (2mg MAX) dose of alprazolam that all the alcohol does is make the benzos kick in harder. I dont end up stumbling or pass out.

Today i took 1mg alprazolam, and then a half our later 32 oz of beer on a near-empty stomach and didnt feel anything past the benzos kicking in. ??

From past experience ive noticed my brain and or my drug metabolism is way drifferent than anyone I know except some family. Drugs in general last longer on me, and pot for example does the exact opposite of what most stoners get from it. Instead of relaxation i get stimulation, etc. Im a bit hypersensitive to all stimulants. Hydrocodone can last for up to ten hours on me. I'm always the last guy awake cracked out on acid...etc.

Also on that note, generally when im sober a beer wakes me up, and if I am anxious alcohol actually seems to worsen it or do nothing but make me feel like shit.

Anyway...I am looking for any type of pharmacological insights on the alprazolam and alcohol thing. I was thinking that since apparently ethyl alc is a gaba-a agonist yet binds at a different site on the receptor protein maybe that has something to do with it? I really dont know...hoping someone will.

Maybe i just think I'm not drunk but am? I really dont think thats the case as in situations described above i end up driving people completely straight, yet maybe over the legal BAC, at the end of the night when theyre all goofed out from the same amount of booze ive had and could never drive.

enlighten me, shame me, whatever, like arnold said...DO IT!!!!


----------



## Hammilton

If I'm not mistaken, alcohol has important effects involving benzodiazepine binding sites, a1 or 2, primarily, no?  I believe alprazolam has highest affinity for a1 subunit containing GABA-A receptors.


----------



## shibireru

How likely is it that serotonin syndrome should occur following the administration of these combinations of serotonergics:

1.  5mg of Pindolol (Unlike certain other beta-blockers, it's an antagonist at the 5-HT1A _autoreceptors_ only... supposedly) + 100mg of Nefazodone (SNRI, 5-HT2A antagonist, and alpha 1 antagonist)  + 100mg of 5-HTP

2.  5mg of Pindolol + 100mg of Nefazodone + 10mg of Citalopram

3.  5mg of Pindolol + 10mg of Citalopram

Is any of these acceptably safe?  I'm thinking that only the third is - if that.

I've been taking Pindolol and Nefazodone for the past three days and I feel like garbage.  I had had such high hopes that I had finally found a winning combination, but so far (granted it's too early to be drawing any sound conclusions) it's looking like I'll never get better.  This was pretty much my last attempt.  I've already tried dozens of medications and nothing's worked.  Fuck this!


----------



## e n d e r

mr.dopeman said:


> Does anyone know the solubility of THC and other cannibinoids in solvents such as ethanol, isopropyl alcohol, and acetone. And specifically at spefcific temepratures. Are Thc and any other of the cannibinoids insoluble in any of those solvents at a temeprature achivable in a freezer?



Probably not.   I think the solubilities are too high to get any one of the cannabinoids to come out of solution.   You're also trying to isolate a compound from a mixture of similar compounds that are capable of solubilizing each other.   When you concentrate the solutes, you inevitably end up with an oil.

One strategy might be to modify the solubilities of the cannabinoids by derivatizing them.   You can isolate CBN-acetate after reaction of hemp oil with acetic anhydride.  The hydrolysis of that isolated product gives cannabinol. 

Could make the 3,5-dinitrobenzoate ester derivative by reaction with 3,5-dinitrobenzoyl chloride in pyridine....or the 3,5-dinitrophenylurethane derivative by reaction with 3,5-dinitrobenzoyl azide.  

A more recent patent suggests replacing the azide with an isocyanate to make the crystallizable THC carbamate that could be hydrolyzed back to THC.


----------



## Yopreacher

In the  Antidepressants and Recreational Drugs (long!) FAQ there is the claim that mirtazapine potentiates hallucinogens like LSD. But to my knowledge (I could be wrong) mirtazapine is an antagonist at 5HT2a and the hallucinogenic effect of LSD is very often attributed to LSD being a 5HT2a agonist. And 5HT2a antagonists blocks the hallucinogenic effect of LSD.

Why then does mirtazapine potentiate LSD?


----------



## macropsia

What effect, if any, might selective D2 antagonism have on prolactin?


----------



## bantaren

Today at 10 am I took one 36 mg Concerta (methylphenidate OROS formulation). Will the EFFECT still be there at all at 4 pm tomorrow?


----------



## nuke

Probably not.  The extended release tablets are designed to progressively release the drug throughout the day but still allow sleep at night.


----------



## nuke

macropsia said:


> What effect, if any, might selective D2 antagonism have on prolactin?



Marked elevation of prolactin levels.


----------



## ebola?

Would selegiline be useful for making the day after MDMA more bearable, or would it simply slow the catabolism of alpha-methyl-dopamine, making the crash worse?
(note, I am not saying that selegiline should be combined with MDMA).

ebola


----------



## Hammilton

alpha-methyl-dopamine's biggest issue is the gluconuride metabolites (I think I have that right, it is amDA's metabolites that's the problems).  I don't know if it's targeted by MAO, but if it is, then yeah, if you block that metabolic route, then more will be turned into the gluconuride.

I doubt it'll do anything beneficial for the crash though.

Also, unless you take a pretty high dose, it won't have much in the way of beneficial effects on 5HT.

Personally, I'd be worried about remaining MDMA and other metabolites causing problems if you block DA metabolism, because you'll be taking it fairly soon after taking the MDMA I assume.


----------



## macropsia

Does activation of both the D1 and D2 DA receptor subtypes/classes suppress prolactin then? My thinking was that, even if this were the case, antagonizing D2 (which are primarily presynaptically located, no?) would increase DA substantially enough to offset this effect by stimulating D1 as well. Some people find low dose (i.e., D2 specific) amisulpride quite stimulating; even comparable to methylphenidate.

I ask because I'm thinking about trying low-dose amisulpride, possibly with a bit of l-deprenyl, for anxiety/depression and am trying to figure out whether any anti-psychotic-like side-effects are likely to occur due to prolactin increase.


----------



## shibireru

rocknroll714 said:


> Pindolol isn't a selective autoreceptor ligand nor is it a proper antagonist. It affects both autoreceptors and post-synaptic receptors just like any other ligand and it has about 20% intrinsic activity for activating the 5-HT1A receptor making it a weak partial agonist.
> 
> Also serotonin syndrome results from combined and excessive 5-HT1A and 5-HT2A activation. 5-HT2A antagonists (like nefazodone) diminish symptoms and have even been used to treat it.
> 
> For these reasons, I'd imagine those combinations would be relatively safe. You need pretty high levels of serotonin to cause serotonin syndrome anyway. I've taken.. 1 gram of 5-HTP without any ill effects (cept nausea) and 20 grams of L-tryptophan without any issues either (cept even worse nausea). I've taken 100 mg of paroxetine acutely with no indications of serotonin syndrome either. From what I hear you need something like 300 mg/kg of an SSRI for it to be fatal.




Thanks for the response.

I am aware of much of that, but things are perhaps not quite so simple.

Firstly, Nefazodone is a NRI meaning that it could well exacerbate serotonin syndrome or make it more liable to occur.  Secondly, it is presumably an antagonist at 5-HT2A autoreceptors as well as post-synaptic 5-HT2A receptors and in this it perhaps has a proclivity to dispose a person taking it to the development of the condition just as much as it has the capacity to mitigate or prevent the condition (depending on the density and sensitivity of 5-HT2A receptors, pre-synaptic and post-synaptic, of the individual taking it).  Thirdly, I've read reports about it being one of the serotonergic medications most liable to cause serotonin syndrome.  And then on top of all this, it is an SRI, which of course isn't a good thing as far as serotonin syndrome prevention is concerned.

P.S.

I read your post in which you first reported having taken a gram of 5-HTP and suffered no untoward effects.  Though I knew that this wasn't particularly good for the heart, I decided to personally reprise this act: like you I took a whole gram of 5-HTP, but, unlike you, I had a shitty-ass time.  I felt psychotic and just weird as all hell.  No euphoria.  (For the love of god why can't substances affect me positively the way they do for others!?  Nothing makes me feel good.)  

Just thought I'd share that.


----------



## Bob Loblaw

I made a BDD Dictionary, and I'd like to make sure some terms are properly defined.  (Please keep in mind this is intended for a basic crowd.)


*NSFW*: 



*Affinity*- Force that impels certain atoms or molecules to bind to or unite with other atoms or molecules to form complexes or compounds; chemical attraction
*Agonist*- Drug that binds to a receptor in the brain, causing a chemical release
*Antagonist*- Drug that cancels the effect of an agonist, latches onto  a receptor with greater efficiency
*Anticholinergic*- Drug that blocks Acetylcholine; works by competitive inhibition of ACh receptors in neurons
*Bioavailability*- A measure of the amount of drug that is actually absorbed from a given dose
*Blood Brain Barrier*- Naturally occurring barrier created by the modification of brain capillaries that prevents many substances from leaving the blood and crossing the capillary walls into the brain tissue

*Ceiling*- The maximum biological effect of a given drug, regardless of how large a dose is administered
*Competitive Antagonist*- Receptor antagonist that binds to a receptor but does not activate the receptor, will compete with available agonist for receptor binding sites on the same receptor
*Cross-tolerance*- Resistance to one or several effects of a drug as a result of tolerance developed to a pharmacologically similar compound

*Efficacy*- The capacity to produce an effect
*Enantiomer*- One of a pair of molecules that are nonsuperimposable mirror images of each other

*First-Pass Metabolism*- When a drug is administered orally, it passes through the liver before being absorbed 
*Latency period*- Period of time which must elapse between when a dose of drug is taken and the time at which it produces effects
*Ligand*- Molecule that binds to a macromolecule, a ligand binding to a receptor

*Metabolism*- Sum of chemical and physical changes in tissue, chiefly of anabolism (those reactions that convert small molecules into large), and catabolism (those reactions that convert large molecules into small), including both endogenous large molecules as well as biodegradation
*Neurotransmitter*- Specific chemical released by a presynaptic cell that crosses the synapse to stimulate or inhibit the postsynaptic cell; neurotransmitters released by presynaptic cells may change transmitter release from presynaptic cells


*Racemic*- Mixture of an equal number of dextro- and levorotatory substances, which are separable
*Receptor*- Structural protein molecule on a cell's surface or within the cytoplasm that binds to a specific factor, such as a drug, hormone, antigen, or neurotransmitter



I hope this is ok .


----------



## ebola?

Two questions:
1.  Would people be able to 'feel' in vivo whether something is a potent serotonergic neurotoxin, a la 4-chloro-amphetamine?  I mean, MPTP's insta-Parkinsons is rather unmistakable. . .
2.  Does anyone have info on interactions between tramadol and selegiline at maob-selective doses for the latter?

ebola


----------



## MurphyClox

ebola? said:
			
		

> Two questions:
> 1.  Would people be able to 'feel' in vivo whether something is a potent serotonergic neurotoxin, a la 4-chloro-amphetamine?  I mean, MPTP's insta-Parkinsons is rather unmistakable. . .
> 2.  Does anyone have info on interactions between tramadol and selegiline at maob-selective doses for the latter?
> 
> ebola



to 1.: This is rather improbable with regard to objective measurements. I mean, there are always certain people who think that they "feel" something in this respect, but I don't think that such effects are immediately feelable... Even MPTP (resp. MPP+) induced damage needs some time to develop (depending on the dose: ~days, I would think).

to 2.: To my best knowledge does a) tramadol not inhibit neither MAO-A nor -B and b) is not metabolized via any MAO. If the raised 5HT-levels pose a danger in combination with selegiline is a different question, which I'm not able to answer right now.

Peace! _Murphy_


----------



## shibireru

Rocknroll-

Thanks again.



What does it mean if cabergoline does nothing to enhance one's libido?  Could that mean that one had a highly developed prolactinoma?  I've taken about 1.5 mgs this week and it has had only the vaguest positive impact upon my sex drive.  

What are some possible pharmacological causes for hyperprolactinaemia?  I've been taking docosahexaenoic acid and melatonin for months now and I'm beginning to suspect that they may be involved somehow.  I know, for instance, that DHA somehow increases the activity of D1 receptors in the prefrontal cortex (perhaps it upregulates them?).  If it had this effect on adenohypophyseal D1 receptors, it could very well produce a prolactinoma and thus hyperprolactinaemia.  I say this by the following line of reasoning: I read a study which purported to show that cabergoline taken long-term (6 months or so) has the effect of shrinking prolactinomas - which result is retrograde to what intuition would suggest, which is that through homeostatic mechanisms the prolactinoma would become larger to compensate for decreased prolactin production and secretion.  So if long-term D2 agonism can cause the shrinking of a prolactinoma then perhaps long-term D1 agonism can give rise to the hypertrophy of the portion of the adenohypophysis responsible for prolactin production.

P.S.  I've noticed that when I quit DHA and go at least a month or thereabouts without it I notice positive changes in my range of emotions and my libido and that if, having quit for a month, I take just a single dose, I will perceive the onset of low libido and blunted emotions within an hour or two, which both last for at least a week thereafter.


----------



## Artificial Emotion

I didn't know whether to post this here or is Science & Tech. I am doing some research into extracting morphine from poppy pods and have found a lot of interesting articles in journals on Google which I cannot access. How do I get access to these articles? Do I have to pay for every single article (which would cost a fortune) or can I pay a fixed fee so that I can get access to a large number of journals? I don't know anyone I can ask to access the journals for me on my behalf so I have to resort to paying


----------



## ebola?

find a friend with uni access.
use his library's proxy server.

(thanks for answers, all)

ebola


----------



## Artificial Emotion

Forgive my ignorance, but does this mean I have to actually go to someone's university library? That's not likely to happen unfortunately.


----------



## ebola?

nope.
you just have to get an ip and login information from this person.


----------



## Artificial Emotion

Thanks mate.


----------



## permastoned

Why do antihistamines that work centrally often (if not always?) tend to have anticholinergic effects?


----------



## shibireru

permastoned said:


> Why do antihistamines that work centrally often (if not always?) tend to have anticholinergic effects?



Sequence homology and/or structural similarity, I guess.  I know very little about these things, but based on what I know, it seems that the only possible explanation is that antihistamines tend to antagonize the muscarinic acetylcholine receptors due to some similarity (not necessarily very great at all) between the geometry of the histamine and muscarinic acetylcholine receptors.   

Mirtazapine, by the way, is one H1 antagonist that has negligible affinity for the muscarinic acetylcholine receptors.


----------



## vortex30

Explain how Nitrous Oxide is a NMDA antagonist.

Does N2O affect any other receptors/neurotransmitters in the brain?

How is N2O metabolized? 

Is there a dangerous number of 8g chargers not to go over in a single dose? I've done 3 at the most, but was thinking I may want to try 4. Essentially, what is the LD50?

Can you be allergic to N2O?


----------



## permastoned

shibireru said:


> Sequence homology and/or structural similarity, I guess.  I know very little about these things, but based on what I know, it seems that the only possible explanation is that antihistamines tend to antagonize the muscarinic acetylcholine receptors due to some similarity (not necessarily very great at all) between the geometry of the histamine and muscarinic acetylcholine receptors.
> 
> Mirtazapine, by the way, is one H1 antagonist that has negligible affinity for the muscarinic acetylcholine receptors.



That's what I figured. Just it seems that nobody ever points it out or uses data to prove it. I cant do all that computer combinatorial chem or whatever, 3d drug design. Histamine and acetylcholine look quite different to me. But as I said, without the 3d I cant really tell. Dont know how to compare the receptors without a wiki picture either.. and it hasn't been made for the muscarinics.


----------



## Bob Loblaw

Bob Loblaw said:


> I made a BDD Dictionary, and I'd like to make sure some terms are properly defined.  (Please keep in mind this is intended for a basic crowd.)
> 
> 
> *NSFW*:
> 
> 
> 
> *Affinity*- Force that impels certain atoms or molecules to bind to or unite with other atoms or molecules to form complexes or compounds; chemical attraction
> *Agonist*- Drug that binds to a receptor in the brain, causing a chemical release
> *Antagonist*- Drug that cancels the effect of an agonist, latches onto  a receptor with greater efficiency
> *Anticholinergic*- Drug that blocks Acetylcholine; works by competitive inhibition of ACh receptors in neurons
> *Bioavailability*- A measure of the amount of drug that is actually absorbed from a given dose
> *Blood Brain Barrier*- Naturally occurring barrier created by the modification of brain capillaries that prevents many substances from leaving the blood and crossing the capillary walls into the brain tissue
> 
> *Ceiling*- The maximum biological effect of a given drug, regardless of how large a dose is administered
> *Competitive Antagonist*- Receptor antagonist that binds to a receptor but does not activate the receptor, will compete with available agonist for receptor binding sites on the same receptor
> *Cross-tolerance*- Resistance to one or several effects of a drug as a result of tolerance developed to a pharmacologically similar compound
> 
> *Efficacy*- The capacity to produce an effect
> *Enantiomer*- One of a pair of molecules that are nonsuperimposable mirror images of each other
> 
> *First-Pass Metabolism*- When a drug is administered orally, it passes through the liver before being absorbed
> *Latency period*- Period of time which must elapse between when a dose of drug is taken and the time at which it produces effects
> *Ligand*- Molecule that binds to a macromolecule, a ligand binding to a receptor
> 
> *Metabolism*- Sum of chemical and physical changes in tissue, chiefly of anabolism (those reactions that convert small molecules into large), and catabolism (those reactions that convert large molecules into small), including both endogenous large molecules as well as biodegradation
> *Neurotransmitter*- Specific chemical released by a presynaptic cell that crosses the synapse to stimulate or inhibit the postsynaptic cell; neurotransmitters released by presynaptic cells may change transmitter release from presynaptic cells
> 
> 
> *Racemic*- Mixture of an equal number of dextro- and levorotatory substances, which are separable
> *Receptor*- Structural protein molecule on a cell's surface or within the cytoplasm that binds to a specific factor, such as a drug, hormone, antigen, or neurotransmitter
> 
> 
> 
> I hope this is ok .



I'm just going to bump this .


----------



## permastoned

Bob Loblaw said:


> I'm just going to bump this .



A few changes I would recommend.

An agonist does not always cause a chemical release. Rather, you can say that it will initiate a cascade of reactions within the target cell. Additionally, I hate to be picky, but it is not always a drug, by saying this you completely disregard endogenous agonists. Additionally, it is not always in the brain

Agonist: Compound that binds to a receptor, activating it and initiating a cascade of reactions within the receptor's cell.

Change drug in antagonist to compound aswell. Your definition of antagonist is actually a competitive antagonist. An antagonist does not have to latch onto the cell with greater efficiency, all an antagonist needs to be an antagonist is to bind to, but not activate the receptor.

as such

Antagonist: Compound that binds to a receptor, but does not activate it.

Then you have competitive antagonist later which is correct

Last thing

First-pass metabolism.. this is incorrect. It can not pass through the liver before being absorbed, I think you mean that after it is absorbed, it passes through the liver before it can reach other tissues in the body (hepatic portal vein).

However, you must realise that second-pass metabolism also occurs in the liver.

A simple way to desribe it (this is as simple as I can make it without killing myself, I hate excluding info. you cut parts out yourself):

The aim of metabolism is to convert fat soluble drugs into water soluble substances that can be excreted by the kidneys;

First-pass metabolism occurs after absorption of the drug from the stomach or intestine, where it flows directly through the hepatic portal vein to the liver. The effect is to alter the drug to reveal or create a new functional group, an example being an oxidation reaction. This occurs in the smooth endoplasmic reticulum of the liver.

Second-pass metabolism, which occurs in the cytosol of the liver, attaches the new functional group to an endogenous water soluble substance, which will allow the drug to be excreted by the kidneys. An example is glucronidation. 




Take what you want from my suggestions


----------



## Bob Loblaw

Thanks a ton :D


----------



## Sturnam

Just making sure I have my information correct:

The new theory for tolerance (at least for opioids) is that the receptor density increases, and that the G-proteins uncouple from the receptors, right?


----------



## melange

*super potent phenethylamine  vasoconstriction*

the bromo-dfly wikipedia states:

"Also, a Swedish man had to have the front part of his feet and several fingers on one hand amputated after taking a massive overdose. Apparently the compound acted as a long-acting efficacious vasoconstrictor, leading to necrosis and gangrene which was delayed by several weeks after the overdose occurred. Several other cases have also been reported of severe peripheral vasoconstriction following overdose with Bromo-DragonFLY, and a similar case is also known from DOB"



is this true?



and  why?


----------



## melange

I guess pressor activities, and long duration?


----------



## Smyth

i dont know for sure, but one time on a high dosage of dob my legs felt painful as hell.

For some reason after i quit smoking the "painfulness" of this drug did not occur although its still a powerful vasopressor and hypertension may be an issue (if u take too much).


----------



## Hammilton

I've seen photos.  Yeah, it's definitely true.


----------



## AshtrayBroom

*LSD changed colour in the bottle*

I was given a small bottle of LSD by a VERY reliable source who said it was colourless initially (as it should be), but after ~4 months in storage (in a drawer in the dark.. 20-25 degrees Celsius approximately it has changed to a dark brown sort of colour. The bottle is made of plastic and sealed well with a plastic lid. There's about 5-6 drops in the bottle, not sure if the quantity is at all relevant. My source has taken it and has confirmed that it is LSD - they have a fair amount of experience to make this judgment.

Basically I'm wondering if in this dark brown state the LSD is fit for consumption, and for an explanation of what has happened to it chemically.

Cheers

(The above is an x-post from the Psychedelic Drug Discussion forum)


----------



## The Monkey Mantra

Put it in the freezer!!!


----------



## permastoned

Activation of serotonin receptors in the periphery causes vasoconstriction.. that is why it was called serotonin in the first place (sero=blood, tonin=increasing vascular tone). It is stored in platelets, in order to cause vasoconstriction at places of injury, to decrease blood loss. Obviously, certain subclasses of the receptor cause the vasoconstriction, and evidently BromoDragonFly is a particularly potent agonist of these receptors.


----------



## nuke

merging to q&a thread


----------



## nuke

merging to q&a thread


----------



## mad_scientist

melange said:


> the bromo-dfly wikipedia states:
> 
> "Also, a Swedish man had to have the front part of his feet and several fingers on one hand amputated after taking a massive overdose. Apparently the compound acted as a long-acting efficacious vasoconstrictor, leading to necrosis and gangrene which was delayed by several weeks after the overdose occurred. Several other cases have also been reported of severe peripheral vasoconstriction following overdose with Bromo-DragonFLY, and a similar case is also known from DOB"
> 
> 
> 
> is this true?
> 
> 
> 
> and  why?



Yes it is true but it is unclear why exactly. 

Bromo-dragonfly is a very potent 5HT2B agonist which is a receptor that causes vasoconstriction, and it is also suspected that some 5HT2A agonist hallucinogens may also be alpha-1 adrenergic agonists given the structural similarity with selective alpha-1 agonists like methoxamine (2,5-dimethoxy-beta-hydroxyamphetamine).

Since alpha-1 agonists are also vasoconstrictors, it seems likely that bromo-dragonfly (and also DOB etc) may cause vasoconstriction via two seperate mechanisms that will be synergistic, so its not surprising the effect can be quite pronounced at high doses.


----------



## mad_scientist

vortex30 said:


> Explain how Nitrous Oxide is a NMDA antagonist.



Open channel blocker, binds in the middle of the pore that usually lets Ca2+ ions through. 



> Does N2O affect any other receptors/neurotransmitters in the brain?



Not directly but NMDA antagonist effect leads to multiple downstream effects.



> How is N2O metabolized?



Pretty sure its excreted unchanged but not sure on this.



> Is there a dangerous number of 8g chargers not to go over in a single dose? I've done 3 at the most, but was thinking I may want to try 4. Essentially, what is the LD50?



The main risk is suffocating from not breathing enough air. N2O is not a strong enough anesthetic agent to produce fatal respiratory depression before it wears off, so fatalities invariably result from people passing out while breathing the pure gas. However regular heavy use of N2O can deplete vitamin B12 which can lead to nerve damage if not treated. 



> Can you be allergic to N2O?



Yes you can be allergic to just about anything so I doubt N2O is any exception.


----------



## LabRatNW

mad_scientist said:


> Yes you can be allergic to just about anything so I doubt N2O is any exception.



The compound has to be able to illicit an immune response for allergy. N2O just isn't big enough.


----------



## permastoned

elicit, and I don't see any reason that an antigen must be any certain size


----------



## shibireru

Can chronic use of MAO-B inhibitors result in the upregulation of the transcription of this enzyme.  I did a google search and found of course that its transcription can be upregulated, I just don't know whether selegiline or rasagiline will do that.


----------



## permastoned

^In my personal experience, yes, it does. But playing with the dosages is in your hands young fellow.


----------



## ebola?

> In my personal experience, yes, it does.



How did you assess so?


----------



## permastoned

I believe the term is amateur 'bioassay'.

I am aware of the subjective feelings of MAO B inhibition and of those of MAO A inhibition; I have been on selective inhibitors for both of the isoforms. As such, when the effect of selegiline decreased (yes, obviously, partially due to Dopamine receptor downregulation,) I increased the dose daily until virtually the same effects as original were reached. At one point I raised the dose too high and could feel the effects of inhibition of MAO A start to creep in (rumbling gut, diarrhoea) etc.


----------



## ebola?

No one would answer this in OD:

"Lets say that you have two hypothetical drugs, each inducing the same degree of monoamine release IN SUM. However, drug 1 releases a moderate amount of dopamine, a large amount of 5ht, and a moderate amount of NE, while drug 2 releases a large amount of dopamine, a moderate amount of 5ht, and a moderate amount of NE. Their durations are identical, as are the levels of compulsion to re-dose, as are the toxcicities of the metabolites.

Which would be more neurotoxic? What is the bottleneck in the pathological uptake of DA by SERT, the amount of intercellular dopamine or the number of SERT that have 'spat out' serotonin, leaving them open to reuptake of dopamine?

ebola"


----------



## nuke

A greater amount of dopamine/norepinephrine release along with moderate serotonin release is probably worse (eg methamphetamine, which is much more toxic than MDMA).

The uptake of DA by SERT is kind of hard to characterize:


> Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin transporter-mediated dopamine uptake
> 
> Shannon N. Saldaña and Eric L. Barker
> 
> Although studies have suggested that dopamine can be transported by serotonin transporters (SERTs), such activity has not been characterized at the cloned SERTs. Dopamine and serotonin uptake by human SERT expressed in HEK-293 cells was compared at 37 and 40 °C. Elevated temperature was found to alter serotonin transport, but had no significant effect on dopamine transport. These effects led to a 10-fold increase in the serotonin:dopamine transport ratio reflecting an increased preference of SERTs for dopamine as opposed to serotonin at the higher temperature. The effects of 3,4-methylenedioxymethamphetamine (MDMA) on SERT-mediated dopamine transport were also evaluated by pre-incubating SERT-expressing cells with MDMA. The presence of intracellular MDMA caused a decrease in [3H]dopamine uptake but had no effect on [3H]serotonin transport suggesting that intracellular MDMA may be capable of inhibiting transporter function.



I'm guessing for acute neurotoxicity like that of methamphetamine you need elevated temperatures from 5HT release and a large amount of DA and NE release.  I'm not sure the intracellular concentration of 5HT had much to do with it.


----------



## permastoned

> eg methamphetamine, which is much more toxic than MDMA


 Doesn't it also have a lot to do with the specific metabolites of the drug?


----------



## nuke

permastoned said:


> Doesn't it also have a lot to do with the specific metabolites of the drug?



I don't think so.  The main metabolites are p-OH-METH, p-AMP and p-OH-AMP.  The hydroxylations I believe are mediated by hepatic P450 enzymes.  The effect on catecholamines and serotonin (high amounts of radicals generated by MAO degredation under elevated temperatures destroying mitochondrial DNA and forming toxic metabolites of the endogenous neurotransmitters) is probably more responsible for the neurotoxic effect.  I'd be willing to bet that any potent releaser of all three monoamines may cause neurotoxicity.


----------



## permastoned

> I don't think so. The main metabolites are p-OH-METH, p-AMP and p-OH-AMP. The hydroxylations I believe are mediated by hepatic P450 enzymes. The effect on catecholamines and serotonin (high amounts of radicals generated by MAO degredation under elevated temperatures destroying mitochondrial DNA and forming toxic metabolites of the endogenous neurotransmitters) is probably more responsible for the neurotoxic effect. I'd be willing to bet that any potent releaser of all three monoamines may cause neurotoxicity.



I'm fairly sure that this isn't the case. Some releasers, for example the aminoindans show promise with their lacking neurotoxicities:

Re http://en.wikipedia.org/wiki/Indanylamphetamine



> This indanylamphetamine, (also called IAP, 1-(5-Indanyl)-2-aminopropane or 5-(2-aminopropyl)indane) is an analog of MDA, but with both oxygens in the methylenedioxy bridge replaced by methylene (CH2) units. It has been shown to not be a serotonergic neurotoxin, and is active at 0.2 mg/kg in Nichols' lab rat tests, compared to 0.8 mg/kg for MBDB. However, the lab rat results show that the effects should be somewhere inbetween MDA and MBDB, as it doesn't fully substitute for the purely serotonergic compound MMA (3-Methoxy-4-Methyl- Amphetamine), but does share some of the dopaminergic effects of MDA. Further animal tests showed that IAP does not substitute for amphetamine, so the compound is not a particular stimulant either. IAP is also one of the most active serotonin-releasing agents known so far, together with the 4-iodoamphetamine and 4-methylthioamphetamine (4-MTA). However, 4-iodoamphetamine is a serotonergic neurotoxin, and 4-methylthioamphetamine has also shown signs of toxicity, as it also exhibit MAOI properties. This together with is serotonin-releasing properties, makes it prone to give a serotonin syndrome in people taking it, and several 4-MTA related deaths has been reported. The same cannot be ruled out for IAP, so caution is advised in any human testing of this compound. The animal test results suggest that the active dose is somewhere between 20-40mg. In October 1998, there were news reports that the compound had been seized together with other ecstasy-like compounds in South Australia (possibly Adelaide), confirming that it has been manufactured in clandestine laboratories there.



Or the closely related napthylamphetamine, http://en.wikipedia.org/wiki/Naphthylaminopropane.



> Naphthylisopropylamine (PAL-287), or naphthylaminopropane (NAP), is a psychoactive drug and research chemical currently under development for the treatment of alcohol and stimulant drug addiction. It functions as a non-neurotoxic and well-proportioned serotonin, norepinephrine, and dopamine releasing agent.[1]


----------



## nuke

If I recall right IAP is not strongly catecholamine releasing.

Monoamine oxidase inhibitors are well known to be preventative in neurotoxicity due to their ability to inhibitor production of hydrogen peroxide, so 4-MTA doesn't count.

If that naphthylisopropylamine compound binds with high affinity for the 5HT transporter and with strong competition, it may prevent the reuptake of amines into the neuron and in doing so their deamination by MAO.  Notice METH and MDMA release 5HT at far lower concentrations than they bind to SERT.  My guess is that's the case given the structure of 5HT and the naphthyl substituent being closer to it in terms of size than the phenyl substituent.  This could be the case with IAP as well.  It could also be a 5HT2A antagonist and prevent neurotoxicity via that route as well.

But that naphthyl group may prove carcinogenic yet, so I'd be cautious.

Edit: This paper is kind of dubious too (naphthylisopropylamine):
"Increasing evidence indicates that SERT sites are involved 
in the mechanism by which fenﬂ  uramine increases the risk 
of developing PPH (for review, see Rothman and Baumann 
71  and references therein). For example, medications that 
increase the risk for PPH have in common the ability to 
release 5-HT by a SERT-mediated process. On the other 
hand, not all 5-HT releasers are associated with PPH. The 
antidepressant trazodone is not associated with PPH, yet its 
major metabolite, mCPP, is a potent SERT substrate, as 
noted above. 2  Experimental data from a mouse model of 
hypoxic pulmonary hypertension suggest that 5-HT  2B   recep-
tors may also contribute to the pathogenesis of PPH. 77   The 
relevance of these ﬁ  ndings to drug-induced PPH is not clear, 
since aminorex, a 5-HT releaser that caused an epidemic of 
PPH in the 1960s, 78  has minimal activity at 5-HT  2B   recep-
tors. Viewed collectively, the available data suggest that it 
should be possible to develop dual DA/5-HT releasers 
devoid of fenﬂ  uramine-like adverse effects. In particular, 
we have suggested that a lead drug molecule should be 
chemically distinct from the phenylethylamine structure 
shared by amphetamine-like agents and should lack signiﬁ  -
cant agonist activity at 5-HT  2B   receptors. 79"

Great, it's too bad they didn't bother going through the literature to find out mCPP is also a 5HT2B antagonist.

Aminorex is a 5HT releaser and 5HT is well known to cause PPH.  What's their point?

"Viewed collectively, the available data suggest that it 
should be possible to develop dual DA/5-HT releasers 
devoid of fenﬂuramine-like adverse effects."

Not really, at least not from any of the data you provided.

Aside from that, "The data in Figure 7 show that PAL-287 does not support self-administration 
behavior."  Doesn't sound like it's much fun.


----------



## roastedtoe

*anhydrous ethanol*

Hmm...

...opinions pls, facts even, if you have them. 

It's possible to make acetone anhydrous by adding magnesium sulphate ( ie cooking epsom salts to ash in the oven lol)...I know this from Le Junk's long and wonderful thread.

I wonder, given the difficulty in obtaining ethanol in the UK...

Who here thinks it would be possible to make 95% Alcohol (ie ethanol) by adding mag. sul. ash to a bottle of strong vodka, or a spirit like that, to let it draw out the water in the same way it does in acetone?

The highest proof bottle of spirits I can find in the shops is 80%.  And while you can order ethanol from chemical companies online...once you include the cost of shipping it's about £50 for 100ml. 0_0.

Other option is to home distill a strong spirit...but just wondered if there was a potentially less explosive method! 

Cheers


----------



## Captain.Heroin

Why do you need a high proof liquor?


----------



## roastedtoe

Hi....do perform the full A/B extraction and get the charlie out of the nose garbage.

If it's possible to extract the water from a 80% bottle of liquor it will be better than home brewing up some. lol


----------



## djsim

==> Advanced Drug Discussion


----------



## ingannilo

I want to say that you can actually make them (water and alcohol) separate with salts, but that was from some youtube chemistry bit I watched years ago, may not have been legit.  May have been methanol, too, not ethanol.

The obvious and easy way to do it if you've got any access to glassware is distillation.  The trick is gentle heat to avoid making a bleve out of your home with exploding alcohol vapors.

PS--BLEVE: boiling liquid expanding vapor explosion.


----------



## nuke

Yes, you can dry ethanol solutions to 95% using MgSO4.  It takes quite a lot of it, though.


----------



## roastedtoe

Thanks for confirming my suspicion that it was possible.

Any idea on amount of MgSO4 required?  

For example, if you had a 750ml bottle of non-flavoured 80% spirit, what amount of MgSO4 would you need to make it ethanol 95% and how long do you think it would take?

This seems to me a much safer option than home distilling on the stove, lol, and gets around the expense of purchasing it from an online chemical supplier.

Many thanks.


----------



## nuke

You'll have to do the math...  One mole of MgSO4 can ideally absorb 6-7 moles of H2O if completely dry.  Probably a good idea to overshoot by 25-50%.

It shouldn't take that long, within the span of 1-15 minutes with stirring I'd guess, depending on the granule size (smaller would be faster).


----------



## roastedtoe

ty mate.

this sort of math has never been a strong point for me.  I will do some googling to see if I can work out the calculation...failing that...I'll dump a sh*tload of well baked epsom salts into the bottle and see how I go. Then filter and bottle swiftly...with plenty of ventilation.

Precision.  We demand nothing but precision. lol

All the best.


----------



## ebola?

> Precision. We demand nothing but precision.



I will typically request accuracy as well.


----------



## roastedtoe

Well I was mocking myself with the precision comment. 

A good hydrometre will simplify things on the math front...."is it there yet?"..."is it there yet?".

Cheers


----------



## Jug

*Grapefruit Juice and MAOI's*

Would Grapefruit Juice interact with MAOI's like Phenelzine (Nardil) or Tranylcipromine (Parnate) in a good or bad way... Or not at all?

And how much Grapefruit juice do you need to enhance Xanax 700ml?.. The more the better I guess how much time should I post ingest the grapefruit juice before the Xanax

Regards


----------



## nuke

If they're substrates for CYP 3A4, then it might halt their clearance and raise plasma levels of the drugs.

What is Xanax 700ml?  That's not a dosage, the usual dosage for alprazolam is in the milligrams.

I'd guess a cup or two an hour before would yield effects.


----------



## ebola?

mmm...Would mirtazapine's antagonism at 5ht2c knock-out or reduce drastically mcPP's agonism at that site?

More generally, what sort of difference between binding affinities is necessary for one drug to block another's effects?


----------



## nuke

I'm not sure.  My guess is it would diminish the effect of mCPP's agonism.  Look at their affinity for the receptor to figure out which is a better competitor.  If they both bind equivalently (which I doubt) then they would both compete with 5HT equally and you'd get an equal mix of activity theoretically.


----------



## sdripper

*Stimulants and blood sugar*

Which way do Stimulants like Cocaine/Amphetamine affect your blood sugar?

Do they send it through the roof, or through the floor?


----------



## Lupus

Both

Your body is going to release stored sugars and then eventually crash from not eating/higher levels of insulin.

We really need a stimulant mega thread, this is like the 6th or 7th thread about the negative effects of AMPs this week.


----------



## almost-

Does 4-Methyl-5-phenyl-2-oxazolidinone have any stimulant properties?  It's a metabolite of 4-methylaminorex. And readily available.


----------



## sdripper

So first your blood sugar level soars from stored sugar being released , and then it drops from an insulin response?

 Is the insulin response abnormal because of the stimulant?  As in, a hyper insulin response, therefore sending your blood sugar through the floor, causing a potentially sever hypoglycemic state?


----------



## Buddy122

Im curious to know about this as well.  The first time i ever took E i hadn't eaten the entire day, took it, then got really sick later...which i was told was due to my extremely low blood sugar from not eating all day.  Now I always eat at least a little something right before i take any stims.


----------



## chompy

try eating bananas


----------



## Hammilton

almost- said:


> Does 4-Methyl-5-phenyl-2-oxazolidinone have any stimulant properties?  It's a metabolite of 4-methylaminorex. And readily available.



Quite likely.


----------



## ebola?

nuke said:
			
		

> Look at their affinity for the receptor to figure out which is a better competitor. If they both bind equivalently (which I doubt) then they would both compete with 5HT equally and you'd get an equal mix of activity theoretically.



Ah.  This is what I surmized...but how close together must the binding affinities be for them to be 'equivalent'?  How do other factors, like size of dosage, bioavailability from given route of admin, and propensity to cross the BBB factor in?

ebola


----------



## nuke

> Ah.  This is what I surmized...but how close together must the binding affinities be for them to be 'equivalent'?  How do other factors, like size of dosage, bioavailability from given route of admin, and propensity to cross the BBB factor in?
> 
> ebola



Okay, back to theory...

You have two compounds, X that has an IC50 of 2mM and Y that has an IC50 of 4mM.  Therefore, to get the same amount of displacement of the substrate you would need double the amount of Y as you would X.  So if you consumed 1mmol of X and 2mmol of Y, you should get an equal amount of competition in theory.  So you can see, the binding affinities should probably be within ± 10% of each other to be considered equivalent (just as a thrown-out there rule).  Since such a similarity is generally unlikely, you should easily be able to see who the more competitive compound will be.  

To actually figure out the exact concentration in the brain would be tricky.  I'm guessing the most reasonable way would be to make a radiolabeled version of the compound and run it against a known control with some sort of imaging like PET.  There are calculations for blood barrier penetration but in my opinion they're not extremely accurate and fail to take into account factors such as active transport of the molecule into the brain by amino acid transporters.  Another problem is active metabolites that may also play a role in the activity of the compound.

A program to assist in the calculation of BBB penetration via TPSA is here: http://www.daylight.com/meetings/emug00/Ertl/index.html

Once you get into the activity, that's also fairly obfuscated by the fact that despite direct agonist/partial agonist/antagonist/inverse agonist activity there are also downstream modulators of activity which may be targeted by a given compound or its competing compound.  For instance, while a molecule may be a substrate for the dopamine transporter and cause dopamine release, however it may also have an affinity for the 5HT1A receptor as an agonist that would cause it attenuate the dopamine release (at least in the striatum).  Not to mention other factors like receptor isoforms, which are very common, that could alter the binding cavities of the receptors themselves and therefore modulate the binding affinity of a compound in unpredicatable ways.

There are so many variables involved that to say exactly what to expect from a combination of X and Y is extremely difficult -- probably why Shulgin always said that combinations of drugs should be treated as cautiously as a new drug itself.


----------



## permastoned

Hammilton said:
			
		

> Quite likely.



Is this from your steric knowledge/common sense or from personal experience?


----------



## nuke

4FA freebase is a caustic oil.  You should be able to recrystallize the 4FA salt by dissolving it in something that is slightly soluble at a high temperature, then chilling it and filtering it.


----------



## nasir~

nuke said:


> by dissolving it in something that is slightly soluble at a high temperature.


something like water?


----------



## nuke

Possibly, I don't know much about the solubility.  Maybe water and methanol, ethanol, or acetone.


----------



## ebola?

Thanks nuke.
That's the kind of detail that I desired. 

edit: in reference to post on binding affinities.


----------



## Artificial Emotion

How do you clean a buchner funnel/filter? 

Also, I mixed some tap water with some surgical spirit (ethanol and methanol) which went mily white. What caused this to happen?


----------



## nasir~

ebola? said:


> Thanks nuke.
> That's the kind of detail that I desired.




thanks a lot nuke:D


----------



## nasir~

colbert said:


> very soluable in water. instantly.
> acetone too


what was (~) the highest concentration you tried? 

thanks


----------



## almost-

Does benzobarbital have any recreational properties?


----------



## shibireru

What are the neurochemical/physiologic conditions under which opioid dysphoria is most likely to manifest?  Does any of you know from personal experience what substances are like to prime one for such a negative reaction to opioids?

Out of the blue my neurochemistry seems to have changed in such a way that I can't take an opioid without feeling otherworldly despair.  I took a small amount of hydrocodone last week and felt a barely noticeable sense of wellbeing, far far less than that dosage would normally induce, and then upped the dose hoping for better, but far from becoming euphoric I was plunged into some of the deepest blackness I have felt in years.  Since then I tried several other opioids at various low doses and got nothing but sadness and tearfulness out of them.

Very strange to be sure.  I hope this reverses.


----------



## Artificial Emotion

If you filter pod tea with a triple stack of lab filters and then with a 0.2u bottle top Nalgene filter that uses vacuum filtration, only to find that it clogs straight away even after having used the lab filters, what is a good filter to use as an inbetween step so that it doesn't clog? Should one use Celite (diatomaceous earth)?

I've seen lots of different 'types' of diatomaceous earth for sale. Which type is the most appropriate for filtering pod tea?

Also, can you put a buchner funnel (see pic above) in a dishwasher?!


----------



## shibireru

Okay, I gave my question a little more thought and the answer seems to be that my long-term use of phenethylamine has provoked an upregulation of the transcription of the kappa opioid receptor-encoding gene or of the prodynorphin gene in my nucleus accumbens.  Additionally, mu-opioid receptor agonists provoke a release of cortisol which in turn has the effect of releasing dynorphin, the principal endogenous agonist of the kappa opioid receptor.  A downregulation of D2 receptors and the hypofunctioning of dopaminergic neurons within the pleasure centers of my brain on account of the long-term potentiation of glutamatergic projections into said pleasure centers are both also distinct possibilities.

Memantine doesn't seem to help.

Anyone want me for a guinea pig?  I wouldn't mind testing out some of the kappa-opioid receptor antagonists you've synthesized...


----------



## shibireru

P.S.  I would be * very* interested in hearing the results of one of you coke heads experimenting with a combination of a kappa opioid receptor antagonist, like buprenorphine, memantine, and cocaine.  Maybe you could throw in a low dose of amisulpride, too, if you should happen to be feeling especially bold at the time of experimentation.  If that's not one of the most pleasureful experiences of your life, I'll give you - well I don't have much money at all - so $100 is about the absolute maximum that I could afford (and that with a lot of sacrifice.)  If you're not alive, I'll have the $100 buried with your corpse.


----------



## Enkidu

Artificial Emotion said:


> Also, can you put a buchner funnel (see pic above) in a dishwasher?!



That's not a buchner funnel, it's a fritted filter. The glassware will hold up find in the dishwasher.


----------



## ebola?

> Okay, I gave my question a little more thought and the answer seems to be that my long-term use of phenethylamine has provoked an upregulation of the transcription of the kappa opioid receptor-encoding gene or of the prodynorphin gene in my nucleus accumbens.



I'd like to see the information on which you're basing this hypothesis.

ebola


----------



## shibireru

ebola? said:


> I'd like to see the information on which you're basing this hypothesis.
> 
> ebola




http://www.ncbi.nlm.nih.gov/pubmed/17055175

Role of serotonin in the regulation of the dynorphinergic system by a kappa-opioid agonist and cocaine treatment in rat CNS.



> *It has been shown that chronic cocaine increases prodynorphin mRNA in the caudate putamen* and decreases it in the hypothalamus. *In addition, treatment with a kappa-opioid receptor agonist produced the opposite effect on prodynorphin gene expression in these brain regions* and also evoked a decrease in the hippocampus. *It is already known that kappa-opioid receptor agonists decrease the development of sensitization to some of the behavioral effects of cocaine.* The serotonin system has also been shown to regulate dynorphin gene expression and a continuous infusion of fluoxetine induced prodynorphin gene expression in the same pattern as the kappa-opioid agonist (+)(5a,7a,8b)-N-methyl-N-[7-(1-pyrrolidinyl)-1 oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) in the brain regions investigated. It is interesting to note that treatment with a continuous infusion of cocaine produced different effects on this parameter. To determine whether serotonin plays a role in the regulation of prodynorphin mRNA by kappa-opioid agonists or cocaine, rats were treated with the serotonin depleter parachloroamphetamine (PCA). Beginning 24 h later, rats were treated with the selective kappa-opioid agonist U-69593 for 5 days or continuously with cocaine for 7 days and prodynorphin mRNA was measured. Prodynorphin mRNA was decreased significantly in the hypothalamus, caudate putamen, and hippocampus of rats treated with a single injection of PCA. Subsequent to PCA administration the effects of U-69593 or cocaine on prodynorphin mRNA were differentially affected across brain regions. Prodynorphin gene expression was still increased by U-69593 treatment in the hypothalamus and decreased in the caudate putamen. Cocaine treatment still produced a decrease in this parameter in the hypothalamus and an increase in the caudate putamen. In contrast, in the hippocampus, the decrease in prodynorphin mRNA produced by U-69593 was no longer evident after PCA and cocaine, which previously had no effect, now increased it in the serotonin-depleted group. These findings suggest that serotonin is necessary to maintain normal levels of dynorphin mRNA in all of the investigated brain areas and that the regulation of prodynorphin mRNA expression by chronic treatment with a kappa-opioid receptor agonist or cocaine requires serotonin in the hippocampus, but not in the hypothalamus or caudate putamen.




http://www.sciencedirect.com/scienc...serid=10&md5=6e5784c6d7daaff57d281288cabff9f2

Chronic prenatal cocaine treatment down-regulates μ-opioid receptor mRNA expression in the brain of fetal Rhesus Macaque.



> Ribonuclease protection assays (RPA) were performed to quantify μ-opioid receptor mRNA expression in specific brain regions of day 70 Rhesus Macaque fetuses that were exposed to cocaine (3 mg/kg) or saline from days 22–70 of gestation. The content of μ-receptor mRNA was high in the diencephalon and moderate in the mesencephalon. In contrast, μ-receptor mRNA was lightly expressed in areas such as the frontal cortex, striatum and the temporal lobe. The content of μ-opioid receptor mRNA was significantly higher in the diencephalon than in other brain regions (P<0.001; n=4). Cocaine exposure significantly decreased the expression of μ-receptor mRNA in the fetal diencephalon (P<0.05; n=4 in each group). Our data would indicate that prolonged gestational cocaine exposure causes μ-opioid receptor mRNA down-regulation in specific brain regions of the fetus.



http://www.ncbi.nlm.nih.gov/pubmed/16001119

A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats.



> RATIONALE: Kappa opioid receptor (KOR) agonists interfere with the reinforcing effects of drugs of abuse. KOR agonists decrease heroin, cocaine, and ethanol self-administration, and block heroin and cocaine conditioned place preference (CPP) in rats. However, KOR agonists also produce emesis and dysphoria, making it difficult to determine if their effects on self-administration are due to an action on reward mechanisms or are secondary to the drug's direct aversive effects. Assuming that endogenous KOR ligands modulate circuits involved in drug and alcohol reward, selective KOR antagonists can be used to clarify these issues. If KOR antagonists increase drug self-administration then it is likely that endogenous KOR agonists directly modulate drug intake. OBJECTIVES: To determine the effects of nor-BNI, the highly selective KOR antagonist, on ethanol consumption and CPP. METHODS: Thirty-eight male Lewis rats were given free access to ethanol until stable self-administration was achieved. Animals were then administered a single injection of nor-BNI (10 mg kg(-1)) while ethanol intake was monitored. RESULTS: A single injection of nor-BNI induces a long-lasting increase in ethanol consumption, but does not induce a CPP. A high/low split revealed that this effect was primarily due to an increase in drinking in nor-BNI-treated high drinkers, which drank significantly more than saline-treated high drinkers and also drank significantly more when compared to their own pretreatment baseline. CONCLUSIONS: Blocking the KOR system increases ethanol self-administration, suggesting that the decrease in self-administration seen with KOR agonists is due to a direct modulation of reward circuitry.



http://www.ncbi.nlm.nih.gov/pubmed/9435173

[Dopamine release in the nucleus accumbens during heroin self-administration is modulated by kappa opioid receptors: an in vivo fast-cyclic voltammetry study.



> Mu and kappa opioid agonists are known to produce different, and sometimes opposite, effects on several pharmacological and behavioral measures. However, whether kappa agonists can be used to antagonize the reinforcing and putative dopamine (DA)-releasing properties of a mu agonist such as heroin is unclear. With the use of the high temporal and spatial resolution of in vivo fast-cyclic voltammetry to measure changes in extracellular DA in the nucleus accumbens (NAcc), we observed (1) dose-dependent increases in DA in the NAcc during heroin self-administration (SA), (2) that coadministration of the kappa agonist U50,488H with heroin or intracerebroventricular dynorphin A pretreatment significantly depressed the heroin-stimulated DA release during SA, where U50,488H alone inhibited the basal DA release in the NAcc, (3) that coadministration of low-dose U50,488H or dynorphin A significantly increased heroin SA behavior, whereas high-dose U50,488H, which alone did not support SA behavior, reduced or completely blocked heroin SA and (4) that nor-binaltorphimine dihydrochloride (a selective kappa receptor antagonist) potentiated DA release in the NAcc and modestly decreased heroin SA. Taken together, these data suggest that endogenous kappa receptor activation can inhibit mu agonist-induced activation of the mesolimbic DA pathway, which may in turn depress heroin-induced reinforcement.



http://www.ncbi.nlm.nih.gov/pubmed/10391475

The effect of repeated administration of morphine, cocaine and ethanol on mu and delta opioid receptor density in the nucleus accumbens and striatum of the rat.



> The present study was carried out to evaluate the effect of morphine, cocaine and ethanol on the density of opioid receptors in the nucleus accumbens and striatum of rat brain. The animals were injected i.p. with morphine in a single dose 20 mg/kg, or twice daily for 10 days in increasing doses of 20-100 mg/kg. Cocaine was administered in a dose of 60 mg/kg/day following the "binge" paradigm, every hour for 3 h, one day (single treatment) or five days (chronic treatment). Ethanol was administered in drinking water at increasing concentrations of 1-6% v/v, for one month. As shown by receptor autoradiography, single morphine and cocaine administration did not influence the binding density of the selective ligand of delta2 receptors [3H]Ile5,6deltorphin b, but single administration of cocaine decreased binding density of a highly selective antagonist of delta receptors, [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH. Repeated morphine administration decreased the receptor density after both ligands of the delta receptor in the nucleus accumbens after 3, 24 and 48 h, and in the striatum after 24 and 48 h. The density of [3H]Ile5,6deltorphin b binding remained unchanged in both structures following repeated cocaine administration. After repeated cocaine administration either no changes (3 h) or a decrease in the binding of [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH in the nucleus accumbens and striatum were observed after 24 and 48 h. Ethanol did not influence the binding density of [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH and [3H]Ile5,6deltorphin b in the nucleus accumbens and striatum at any time-point studied. In the nucleus accumbens and striatum, no changes were found in the binding density of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol following single or repeated morphine administration. At 3 h after single or repeated "binge" cocaine administration, the binding of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol was not changed in either structure, but after 24 h the density of mu opioid receptors was decreased in both structures. Ethanol given to rats in drinking water decreased the binding of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol at the time of exposure to ethanol, yet in the nucleus accumbens only. Ethanol withdrawal decreased the density of the mu receptor in both structures after 24, 48 and 96 h. The above data indicate that repeated administration of morphine evokes a long-lasting down-regulation of the density of delta1 and delta2 opioid receptors, whereas cocaine affects in a similar way only the delta1 subtype in the nucleus accumbens, and to a lesser extent in the striatum. A long-term intake of ethanol solution down-regulates mu opioid receptors in both structures, but has no effect on any type of delta receptors. Thus changes in the particular opioid receptor depend on the type of drug used. Furthermore, the most profound changes are observed after late withdrawal, which may play some role in maintaining the state of dependence.


----------



## shibireru

http://www.ncbi.nlm.nih.gov/pubmed/18184783

The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system.



> Stress is a complex human experience having both positive and negative motivational properties. When chronic and uncontrollable, the adverse effects of stress on human health are considerable and yet poorly understood. Here, we report that the dysphoric properties of chronic stress are encoded by the endogenous opioid peptide dynorphin acting on specific stress-related neuronal circuits. Using different forms of stress presumed to evoke dysphoria in mice, we found that repeated forced swim and inescapable footshock both produced aversive behaviors that were blocked by a kappa-opioid receptor (KOR) antagonist and absent in mice lacking dynorphin. Injection of corticotropin-releasing factor (CRF) or urocortin III, key mediators of the stress response, produced place aversion that was also blocked by dynorphin gene deletion or KOR antagonism. CRF-induced place aversion was blocked by the CRF2 receptor antagonist antisauvigine-30, but not by the CRF1 receptor antagonist antalarmin. In contrast, place aversion induced by the KOR agonist U50,488 was not blocked by antisauvigine-30. These results suggest that the aversive effects of stress were mediated by CRF2 receptor stimulation of dynorphin release and subsequent KOR activation. Using a phospho-selective antibody directed against the activated KOR to image sites of dynorphin action in the brain, we found that stress and CRF each caused dynorphin-dependent KOR activation in the basolateral amygdala, nucleus accumbens, dorsal raphe, and hippocampus. The convergence of stress-induced aversive inputs on the dynorphin system was unexpected, implicates dynorphin as a key mediator of dysphoria, and emphasizes kappa-receptor antagonists as promising therapeutics.




http://jpet.aspetjournals.org/cgi/content/full/292/2/803



> *Hydrocodone has an affinity (Ki) for the human µ-receptor of 36.4 nM, which is 28 and 20 times greater than its affinity for the delta -opioid and kappa -opioid receptors, respectively (Maguire et al., 1993).*




To summarize the salient and relevant information of these studies:

Agonism of KORs = antagonism of MORs, DORs, and D2 receptors and to the sensitization and upregulation thereof as well as, of course, to the desensitization and downregulation of the KOR and prodynorphin.

Agonism of MORs = downstream activation of D2 receptors and inhibition of KORs, and all the other obvious crap that I needn't explain at all.

D2 agonism = downregulation of DORs, possibly MORs, and upregulation of KORs and prodynorphin mRNA transcription.


Being that I have long been extremely depressed (i.e. paucity or densensitization of MORs, DORs, and/or D2 receptors); that I have abused phenylethylamine on a long-term basis (meaning further downregulation of D2 receptors, DORs, MORs, and upregulation of KORs, and prodynorphin expression); and finally that hydrocodone or one of its metabolites has some considerable affinity for KORs, especially when there is a paucity of MORs and DORs, it is only to be expected that in higher doses hydrocodone should cause extreme dysphoria and depersonalization as it did to me and that in lower doses it would produce only the mildest euphoria, which, again, is exactly what happened.

I further speculate that buprenorphine, a kappa opioid receptor antagonist, and a (partial) mu opioid receptor agonist would be highly apt to produce euphoria in me and very unlikely to produce dysphoria.

I also wonder whether or not it would be beneficial for me to undertake long-term low-dose Salvia Divinorum therapy or low-dose Naltrexone/Naloxone therapy, as horrific as either undertaking should be until the desired upregulation and the desired downregulation occurred.

http://www.ncbi.nlm.nih.gov/pubmed/15464069

Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.



> Biological studies were conducted on (3R)-7-Hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide (JDTic), the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds. *In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticociceptive activity for up to 2 weeks.* When JDTic was administered either s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist, enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course study of JDTic versus enadoline indicated significant antagonist p.o. activity up to 28 days. In contrast, JDTic, s.c., failed to antagonize the analgesic effects of the selective MOP mu-opioid receptor agonist, sufentanil. In the squirrel monkey shock titration antinociception test, JDTic given intramuscularly (i.m.) shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist.




http://www.ncbi.nlm.nih.gov/pubmed/17702750

Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase.



> *Norbinaltorphimine (NorBNI), guanidinonaltrindole, and atrans-(3R,4R)-dimethyl-4-(3-hydroxyphenyl) piperidine (JDTic) are selective kappa opioid receptor (KOR) antagonists having very long durations of action in vivo despite binding non-covalently in vitro and having only moderately high affinities. Consistent with this, we found that antagonist treatment significantly reduced the subsequent analgesic response of mice to the KOR agonist U50,488 in the tail-withdrawal assay for 14-21 days.* Receptor protection assays were designed to distinguish between possible explanations for this anomalous effect, and we found that mice pretreated with the readily reversible opioid antagonists naloxone or buprenorphine before norBNI responded strongly in the tail-flick analgesia assay to a subsequent challenge with U50,488 1 week later. *Protection by a rapidly cleared reagent indicates that norBNI did not persist at the site of action.* In vitro binding of [(3)H]U69,593 to KOR showed that K(d) and Bmax values were not significantly affected by prior in vivo norBNI exposure, indicating that the agonist binding site was intact. Consistent with the concept that the long-lasting effects might be caused by a functional disruption of KOR signaling, both norBNI and JDTic were found to stimulate c-Jun N-terminal kinase (JNK) phosphorylation in HEK293 cells expressing KOR-GFP but not in untransfected cells. Similarly, norBNI increased phospho-JNK in both the striatum and spinal cord in wild type mice but not in KOR knock-out mice. Pretreatment of mice with the JNK inhibitor SP600125 before norBNI attenuated the long acting antagonism. *Together, these results suggest that the long duration KOR antagonists disrupt KOR signaling by activating JNK.*




http://www.ncbi.nlm.nih.gov/pubmed/16184376

Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats.



> RATIONALE: Stress and depression have been linked to relapse of cocaine abuse. Antagonism of the kappa opioid receptor (KOR) has been reported to attenuate some effects of stressors, and antagonism of the KOR has been reported to have antidepressant-like properties. OBJECTIVES: Our objective was to determine whether the potent and selective KOR antagonist, (3R)-7-hydroxy-N-{(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl}-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide (JDTic), can reduce the ability of a stressor (intermittent footshock) to reinstate cocaine-seeking behavior and to have antidepressant-like effects in the forced swim test (FST). METHODS: Male Long-Evans hooded rats were trained to lever-press, reinforced with 0.5 mg/kg i.v. infusion of cocaine, according to fixed ratio 1 reinforcement schedules during daily 2-h experimental sessions. After performance had stabilized, lever pressing was extinguished for 12 consecutive sessions, and doses of 0 (vehicle), 3, 10, and 30 mg/kg JDTic were then administered i.g. to separate groups of 12 rats. Twenty four hours later, the rats were given 15 min of intermittent footshock (0.87 mA, 0.5 s activation time, average inter-activation interval of 40 s) or a 17-mg/kg i.p. administration of cocaine prime followed by a 2-h reinstatement test session. JDTic was also evaluated for its ability to block diuresis induced by the KOR agonist, U50,488H (10 mg/kg, s.c.), during 5-h test sessions beginning 1 h after footshock reinstatement tests to verify its KOR antagonist activity. In the FST, male Sprague-Dawley rats were treated with either nor-binaltorphimine (nor-BNI) or JDTic (both at 0.3, 1, 3, or 10 mg/kg, injected s.c. 23 h before), or desipramine (5.6, 10, or 17 mg/kg, injected i.p. 23, 5, and 1 h before) and placed in a cylinder of water, during which the predominance of immobility, swimming, and climbing were scored during 5-s intervals for 5 min. RESULTS: The 10- and 30-mg/kg doses of JDTic significantly reduced footshock-induced reinstatement of responding previously reinforced by cocaine and significantly attenuated U50,488H-induced diuresis. In contrast, JDTic did not affect cocaine-prime-induced reinstatement. Both nor-BNI and JDTic decreased immobility and increased swimming time in the FST, similar to the antidepressant desipramine. CONCLUSIONS: Depression and stress are two states during cocaine abstinence which users identify as precipitating relapse, and JDTic may have properties which attenuate both.




I wonder whether or not Ketamine is a kappa opioid receptor antagonist.  According to the SAR paradigm, it's not entirely impossible.  It may also be that it is an inducer of c-Jun N-terminal kinases as JDTic is.  This may be shallow and fallacious reasoning, but it seems attractive to conclude that there is some considerable similarity between the pharmacodynamics of ketamine and KOR antagonists based on the fact that they both have the peculiar property of being able to produce an abatement of depression that endures well after the substances have been metabolized and excreted from the body.  Weak support for this hypothesis comes in the fact that the (partial) NMDA antagonist Memantine does not have any antidepressant effect and certainly not one that endures for weeks after a single dose.  So what's the difference between Memantine and Ketamine?  Simply that Memantine only partially antagonizes the NMDA receptor?  Is that the ONLY reason it doesn't have an antidepressant effect at ANY dose?


----------



## shibireru

And so I repeat my offer to be used as a guinea pig.  I would be so glad to give a kappa opioid receptor antagonist a try.  I would give my fucking left arm, in fact.  I can't stand to feel this way even one second longer.  I want to _fucking_ enjoy life again - for the first time in years.  Someone help me, please.


----------



## ebola?

Wow.  Very intriguing.  Thanks.


----------



## Is it Friday yet?

*Cocktails or not?*

Right - I have Mephedrone, Butylone and some Methylone on the way.
Could someone give Noob advice on cocktails eg Don't or if do in what amount and how? I have heard that the right mix is the shizz!
I'm sure this has been discussed before and if there is a thread could someone guide me.

ps this is after I take a holiday from meph. planecrash

Moderators please bump to thread if req.


----------



## ebola?

this is unexplored territory, and mephedrone seems pretty dangerous, so I'd tread w/ caution if at all.  Perhaps beginning with 150-200 mg of substances total.  These also don't sound like the best combos in terms of fx.  All of these compounds are overly stimulating to begin with, so I don't see how they'd be good complements.

ebola


----------



## Is it Friday yet?

Thanks ebola
After Saturday nights little excursion to the darkside I will be treating Mephedrone with a little more respect anyway, but as always in search of repeating that 1st true MDMA experience, I had heard and seen for sale a mixture called 'Bubbles' (don't think this is trade name) and sorry if this violates BLUA. As I understand this is a mix of Methylone and Mephedrone??And as such the buzz is even closer to MDMA 
Anything further ppl???


----------



## nuke

Artificial Emotion said:


> How do you clean a buchner funnel/filter?
> 
> Also, I mixed some tap water with some surgical spirit (ethanol and methanol) which went mily white. What caused this to happen?



That looks like a crucible, not a Buchner funnel.  You can clean a crucible by soaking it in a 70% EtOH solution with a high concentration of sodium hydroxide and then rinsing it off with distilled H2O.


----------



## Enkidu

Enkidu said:


> That's not a buchner funnel, it's a fritted filter. The glassware will hold up find in the dishwasher.



It is NOT a crucible, lol. We're looking at the same pic, right? It's a fritted filter funnel. I wouldn't use NaOH, because it'll eat away at the glass.


----------



## nuke

Yeah.  It's a fritted Buchner/filter funnel.  My bad.  The NaOH will eat away the glass but it takes quite a while.  You can use KOH if you're really paranoid.


----------



## MurphyClox

KOH in isopropanol works for almost all dirty glass ware. The corrosion of the glass' surface by the base is negligible and not important (exception: volumetric glassware loses it's accuracy).

I recommend a wash with acetone first.

- _Murphy_


----------



## almost-

Has 1-(4-Fluorophenyl)-2-methyl-2-aminopropane been tested in humans?






Seems to be readily available.


----------



## nuke

The mono-methylated version is readily available too and as phentermine sucks I can't see it being all that interesting.


----------



## Artificial Emotion

Please forgive my ignorance, but why would it be a bad idea to put my funnel in the dishwasher?!

Also, I selected my 'funnel' from a catalogue that stated quite clearly that it was a buchner funnel, so I can't understand how it can be wrong. It's the same catalogue used by most glassware suppliers in the UK.


----------



## c0rt3x

Has anyone out there tested this amazingly simple method:



> From: DocMercury ® 	15/03/2006 6:24:01 PM
> Subject: QED @ COOH 	post id: 2146316
> G'day all.
> 
> *
> A simple queery of any chemists out there.
> 
> Simple methods for substitution with methyl group / removal of COOH from R?*
> 
> From: Angus Prune ® 	15/03/2006 6:26:43 PM
> Subject: re: QED @ COOH 	post id: 2146323
> 
> *To clarify, do you mean entirely removing the -COOH including the carbon atom, or keeping the carbon and making it -CH3?*
> From: Everyone Loves Iago ® 	15/03/2006 6:28:21 PM
> Subject: re: QED @ COOH 	post id: 2146328
> *
> 
> React with lithium aluminium hydride in presence of ether to make a lithium salt of the acid,.. remove from ether, then in water will produce the primary alcohol. Then reduce the alcohol by any of various means.*
> 
> From: DocMercury ® 	15/03/2006 6:29:06 PM
> Subject: re: QED @ COOH 	post id: 2146332
> 
> >>keeping the carbon and making it -CH3?
> 
> The usual mode a-la-decarboxylation.
> 
> From: hornedrhodent ® 	15/03/2006 6:29:48 PM
> Subject: re: QED @ COOH 	post id: 2146335
> Making biodiesel Doc?
> From: elfram ® 	15/03/2006 6:31:17 PM
> Subject: re: QED @ COOH 	post id: 2146341
> 
> If you mean removal of the -COOH group rather than reduction of the -COOH to -CH3, you need to search on decarboxylation of aliphatic carboxylic acids.
> 
> From: megsy ® 	15/03/2006 6:32:33 PM
> Subject: re: QED @ COOH 	post id: 2146346
> 
> I don't recommend playing with lithium aluminium hydride...super super reactive...
> 
> From: elfram ® 	15/03/2006 6:33:20 PM
> Subject: re: QED @ COOH 	post id: 2146350
> 
> I concur!
> 
> From: Everyone Loves Iago ® 	15/03/2006 6:34:29 PM
> Subject: re: QED @ COOH 	post id: 2146354
> 
> "I don't recommend playing with lithium aluminium hydride...super super reactive..."
> 
> 
> Naturally I assume Doc is a trained organic chemist with the appropriate equipment and skills...
> 
> From: megsy ® 	15/03/2006 6:36:03 PM
> Subject: re: QED @ COOH 	post id: 2146359
> 
> Naturally I assume Doc is a trained organic chemist with the appropriate equipment and skills...
> 
> ...
> 
> I made a rather large mess in the lab 'playing' with that stuff a few years ago...
> 
> From: DocMercury ® 	15/03/2006 6:37:10 PM
> Subject: re: QED @ COOH 	post id: 2146366
> *
> >>Making biodiesel Doc?
> 
> Nah, rocket fuel.*
> 
> From: DocMercury ® 	15/03/2006 6:44:01 PM
> Subject: re: QED @ COOH 	post id: 2146396
> 
> Assume nothing!
> 
> 
> From: DocMercury ® 	15/03/2006 6:58:15 PM
> Subject: re: QED @ COOH 	post id: 2146433
> 
> I wonder if sodium metal would serve the same purpose as LiAlH?
> 
> Or potassium metal? (got that)
> From: the beervatar ® 	15/03/2006 6:58:43 PM
> Subject: re: QED @ COOH 	post id: 2146434
> 
> >>>Or potassium metal? (got that)
> 
> 
> you booked your funeral?
> From: DocMercury ® 	15/03/2006 7:00:41 PM
> Subject: re: QED @ COOH 	post id: 2146439
> 
> I also have some parrafin bottled Barium.
> 
> The Na was all used up making a bath for Mandy Vanstone. (cheap soap)
> From: Angus Prune ® 	15/03/2006 7:00:54 PM
> Subject: re: QED @ COOH 	post id: 2146440
> 
> >>I wonder if sodium metal would serve the same purpose as LiAlH?<<
> 
> Doubtful.
> 
> >>Or potassium metal? (got that)<<
> 
> IT probably would not have the desired effect. But if you want to try, let the neighbours know so they can get a good vantage point when it blows up.
> 
> From: DocMercury ® 	15/03/2006 7:04:12 PM
> Subject: re: QED @ COOH 	post id: 2146454
> 
> Potassium is no worse than sodium (IME), and has a much prettier 'flame'....
> 
> From: PM 2Ring ® 	15/03/2006 11:30:12 PM
> Subject: re: QED @ COOH 	post id: 2147032
> 
> >Potassium is no worse than sodium (IME), and has a much prettier 'flame'....
> 
> Are you sure about that, Doc? I guess you must be, since you possess some K.... I've had plenty of 'hands-on' experience with Sodium metal, but I've never had the pleasure of meeting Potassium in person.
> 
> However, one of the old 'Open Learning' chem shows did a demo of the reaction of the lighter alkali metals with water. They showed Lithium, Sodium, Potassium and Rubidium. The Potassium reaction was definitely more vigorous than the Sodium reaction. Rubidium just explodes on contact with water. IIRC, Caesium & Francium explode on contact with the moisture in the air.
> 
> Also, one of my high-school science teachers had a few personal anecdotes about Potassium. I got the impression that K was much more dangerous than Na.
> 
> This teacher really knew his stuff. Not only was he a co-author of the science textbook, he'd worked as a chemist in industry for more than a decade before getting into teaching. His prac classes were the best. He told us that he liked to use large quantities of chemicals in his demos, so the class could see what was going on, and because he was used to putting a ton or so of stuff into an industrial processing line before stuff begins to come out the other end.
> 
> When he showed us Sodium reacting with tapwater, he used a huge Pyrex beaker and a whole chunk of Sodium. Impressive!
> 
> 
> From: PM 2Ring ® 	15/03/2006 11:33:21 PM
> Subject: re: QED @ COOH 	post id: 2147040
> 
> >I don't recommend playing with lithium aluminium hydride...super super reactive...
> 
> >I made a rather large mess in the lab 'playing' with that stuff a few years ago...
> 
> Tell us the juicy details! I've been fascinated by LiAlH since I first heard about it, although I think I'd be scared to be in the same room with a reaction that used it.
> 
> 
> From: PM 2Ring ® 	15/03/2006 11:34:41 PM
> Subject: re: QED @ COOH 	post id: 2147043
> 
> > Nah, rocket fuel.
> 
> *
> What kind of rocket? Are you planning on going to outer space, or taking a trip to inner space? *
> 
> From: PM 2Ring ® 	15/03/2006 11:46:43 PM
> Subject: re: QED @ COOH 	post id: 2147073
> 
> >React with lithium aluminium hydride in presence of ether
> 
> I wonder how easy they would be to obtain for the likes of Doc Mercury. If he's taken even a fraction of the drugs he alludes to, the guys at the chem supply houses will spot him the moment he walks through the door.
> 
> I know chemical suppliers tend to contact the authorities if they suspect that chemicals are being purchased for drug or explosive manufacture. So where do the speed labs, et al, get their solvents & catalysts these days? Do they bribe uni students & chem factory workers?
> 
> I wonder if there's an actual semi-organized black market in LiAlH, and similar reagents like BBr3? Or even solvents like ether & chloroform?
> 
> From: yempski ® 	16/03/2006 7:20:26 PM
> Subject: re: QED @ COOH 	post id: 2148711
> 
> I'm pretty sure you could also do the job using the Wittig reaction. I'd check, but my trusty copy of Morri and Boyd is more than 2Mm away
> 
> - yempski
> The views and opinions expressed on this forum are those of the individual poster and not the ABC. The ABC reserves the right to remove offensive or inappropriate messages. ABC conditions of use statement.


----------



## c0rt3x

*Chemistry of Barbiturates*

I'm wondering what was the structural most simple active barbiturate. Any suggestions?


----------



## dread

Barbital?


----------



## ebola?

Okay...what is 2-aminoindan's neuropharmacology like.  I know that the empathogenic derivatives does present much dopaminergic action. . .


----------



## almost-

Yes, What is known about the SAR of barbiturates?

All I know is this what I read in an anesthesia article in my language.

It says that C5 must have aryl or alkyl chain of length 4-9 carbons for optimal activity, longer chains will cause seizures. Only one aryl group allowed in C5. Oxygen in C2 can be replaced with sulphur. 

Alkyl groups in N1 and N3 potentiate anesthesia effects. If both N1 and N3 have substitution, compounds will cause seizures.


----------



## c0rt3x

Thank you, {almost-}, very much! ;-)

^^But what about that extremly interesting *COOH --> CH3* issue?^^

If I consider Permastoned's avatar it seems to be quite obviously... :-D

If you don't like to discuss this in "the public" I'd really appreciate it if you PM me. ;-)

I've already tried simple electrolysis wich smelled like it was sucessfull - but my eyes and my brain told me the opposite... ;-)


----------



## shibireru

I realize that this probably doesn't belong even here, but I can't bring myself to make an appeal to BDDers.  They don't have the wherewithal to even begin to provide sound advice, but that wouldn't stop them from responding with all kinds of asinine and obvious suggestions.  It would be a complete waste of my time.

Okay.  _crosses fingers_

In the past couple of weeks I have greatly increased the amounts and regularity of my consumption of diazepam and lorazepam in order to control my anxiety and I have already reached the point where, when the drugs are eliminated from my system, I experience severe rebound anxiety and insomnia - severe enough that I can not get a single minute of sleep.  On the other hand, all the hypnotics that I can think of interfere with sleep architecture so that, while they do get one to sleep, they make one feel the next day as if he had gotten none at all.  This seems to be especially true of the benzos I am taking.  

So, I must use them and I must not, and I haven't gotten good sleep since I started taking them and my sleep debt is great enough at this point that I feel as if I were about to break and lose all contact with reality.  It's getting worse and worse by the day and I'm becoming more and more mentally and emotionally unstable.

Is there a _*single*_ fucking hypnotic that's commercially available that doesn't interfere with sleep architecture and allows one to get deep and restorative sleep?  (I wish I had the knowledge and skills necessary to synthesize gaboxadol!)

I went to a number of doctors in my area and, surprise suprise!, none of them was able to offer any help.  Ignorant gits.

The only things I've been able to come up with myself are cyproheptadine and trazodone and both of those look more than a little bit scary.  Trazodone frequently causes akathisia and I seem to have a proclivity to experiencing that - severe forms of it too.

Please.  I need some suggestions here.

/No diphenhydramine, alcohol, zaleplon, zolpidem, zopiclone, melatonin, ramelteon, tasimelteon, etc...  All of it is shit


----------



## macropsia

Agomelatine?

MT agonist like ramelteon, plus bonus 5-ht2c antagonism which might be helpful for anxiety. That said, if ramelteon was of little use, then agomelatine might not be either. But if the 5-ht2c antagonism is able to reduce anxiety somewhat and thus the need for benzos, then part of the self-reinforcing cycle of anxiety and sleeplessness can possibly be considered reduced.


----------



## Hammilton

could always go the micheal jackson route.  If you can't sleep with propofol, something is off.

seriously though, bromomelatonin is interesting, and an effective aneasthetic, but I believe it it's quite safe, unlike propofol.


----------



## hamhurricane

*Drug rape myth exposed as study reveals binge drinking is to blame*

http://www.dailymail.co.uk/news/art...veals-binge-drinking-blame.html#ixzz0R2PXisds

its very annoying to me that there are no refrences in this article, a search on pubmed turned up nothing. does anyone know what study is being discussed in this article???


----------



## Hammilton

Not sure, no one is even quoted.  I don't doubt it though.  By now it's well known that alcohol is primarily responsible.

Pubmed shouldn't be your first search for a recently published article from the UK.


----------



## permastoned

shibireru, the answer to your woes is pregabalin. Trust me. Take a good (at least 500mg) dosage and you will be happy as larry, and sleep is deep, refreshing, and restorative. Be careful though, because it can be addictive. And space your usage out by at least 2 days between each use otherwise it will lose its effect, although in ur condition you may have to dose it constantly.

One thing to take note of is that after ingestion, it will take 2 hours to have an effect. I know this because I have seen it in myself and my friends every time we take it. It obviously has a very slow action in the brain. 

If you want to extend ur usage of this drug, it is excreted almost 100% in urine, so you can either drink any urine that you produce to extend the action of the drug, or you can freeze your urine in order to use the drug another day (it is fucking expensive). 

I know of an online site from which you can order it, if you need assistance then pm me. Trust me, this really is the answer to your woes. It kicks benzo's in the ass for sure.


----------



## Sturnam

Does anyone know the mechanism by which NMDA antagonist tolerance develops?


----------



## Rectify

Is an aryl nitro group (Ar-NO2) stable under acidic conditions, under basic conditions, under either acidic and basic conditions, or under neither acidic nor basic conditions?


----------



## ebola?

re: 2-amino-indane (sp?):

A cursory search for articles indicated 'partial generalization' to d-amp in animal experiments.  Does this indicate anything in terms of neurological action?

Well, anything more interesting than, "It shares qualities with other stimulants!" 

ebola


----------



## Hammilton

Rectify said:


> Is an aryl nitro group (Ar-NO2) stable under acidic conditions, under basic conditions, under either acidic and basic conditions, or under neither acidic nor basic conditions?



Stable enough, though this depends loads on the compound in question.

nitrazepam- stable.

trinitrotoluene - unstable.


----------



## shienar

I need some help, i have the tools just not the knowledge. Im hoping someone can help.

A mate ordered some JWH-018 and we eyeballed doses, just popped what looked to me well below a mg onto a cone and smoked it. We got stoned but we dont know whether it was the green or the white.

Now its a white powder with rather sticky properties. It is far more methanol soluble then acetone. 25mg in 4 mls of acetone wouldnt dissolve but after adding .5ml MeOH it dissolved. Now for your view pleasure i have a fuck off saturated hplc trace, it was run under a EPS C18, with acetonitrile / h2o + 0.01% TFA.






Now the envelope that it was sent in had clear signs that it had been opened prior to me receiving it. The side had been razored and then tapped. Im not sure if this was quartine or a posty. 

Any opinions welcome. 

Also the place that sent it, returned the payment. Im not sure as to the bearing of this but i feel its worth mentioning.


----------



## vecktor

the UV spectrum of JWH-018 is available in the THCpharma spice analysis paper, though most JWH compounds will have practically identical UV spectra.
the chromatographic system conditions are also in the paper. I'm sure they used C18 Reverse phase some kind of commercial ODS column and AcN water mobile phase, so with a very small amount of work the conditions can be duplicated then the material identified by retention time.
you will of course need to reduce the sample loading by about 10-20 times to get decent peak shape and a sensible height.
also dissolve the sample in the starting mobile phase don't use additional solvents because they screw things up.


----------



## Phineas Gage

You also might want to get the chromatogram up a bit higher than 190 nm.....say about 280 to 350 nm....looks like you have a maxima around 325 nm.  Try that.  (Since you've used diode array, you can probably extract that chromatogram from your existing datafile.) You'll have lower response = less saturation of the peak & less baseline drift.  Once you get above 220 nm, you can start using acetate buffer with your AcN and still have a flat stable baseline.


----------



## MurphyClox

hamhurricane said:


> http://www.dailymail.co.uk/news/art...veals-binge-drinking-blame.html#ixzz0R2PXisds
> 
> its very annoying to me that there are no refrences in this article, a search on pubmed turned up nothing. does anyone know what study is being discussed in this article???



The article in question:

Hywel Hughes, Rachael Peters, Gareth Davies, Keith Griffiths
" A study of patients presenting to an emergency department having had a 'spiked drink' "
_Emerg Med J_ *2007*, 24, p.89
DOI: 10.1136/emj.2006.040360 


> *Abstract*
> *Objectives:* To assess the scale of drink spiking in our area and identify which drugs are being used to spike drinks and also to assess whether there is a problem with drink spiking in any particular establishment.
> 
> *Methods:* A prospective study of all patients presenting to an emergency department with alleged drink spiking over a 12-month period. Samples were analysed for levels of alcohol and drugs of misuse. Information was collected as to where the alleged spiking took place and the involvement of the police.
> 
> *Results:* 75 patients attended with alleged drink spiking over the period of 12 months. 42 samples were analysed and tested positive for drugs of misuse in 8 (19%) cases. 65% of those tested had alcohol concentrations >160 mg%. The alleged spiking took place in 23 different locations, with 2 locations accounting for 31% of responses. Only 14% of those questioned had informed the police.
> 
> *Conclusions:* Most patients allegedly having had a spiked drink test negative for drugs of misuse. The symptoms are more likely to be a result of excess alcohol.



Full article requests can be placed as usual.

Cheers! _Murphy_


----------



## almost-

http://www.erowid.org/library/books_online/future_synthetic/future_synthetic.shtml

what is that bis-methamphetamine?


----------



## Swerlz

I want to say it's an impurity of meth manufacture. atleast that's what my searches say it is.


----------



## ebola?

Would the stereoisomer fairy exist for chemists working in 4 spatial dimensions?

ebola


----------



## dread

In 4 spatial dimensions yes, along with a whole bunch of other faeries.


----------



## phase_dancer

bis = 2. Bis methamphetamine (Bis-(1-phenylisopropyl)- methylamine) contains 2  meth molecules joined at the amine(-NCH3-NCH3-). It's a known impurity with the Leuckart route.


----------



## bean93

I'm kind of new to Bluelight so hello every one! Wasn't sure whether to post in here but here it goes;
Could you theoretically use methionine in the methylation process to change phenethylamine to methylphenethylamine (which i believe to be amphetamine?) or would you need another reagent such as iodomethyl, and also how would one go about doing this?
I've been doing a lot of research on the internet about it and can't really find much about it other than a mention in PIHKAL, it just seems strange no-one has experimented with this.


----------



## melarsoprol

*Simple chem questions*

Didnt know where this went, but i think OD is appropriate.

Some of you may know that you can cook epsom salts, turn it into anhydrous MgSo4 and put it in industrial solvents (acetone) to make the acetone anhydrous.

Can this procedure be done with OTC isopropol alcohol? would adding mgso4 into the solvent create anhydrous isopropyl alcohol


----------



## vecktor

bean93 said:


> I'm kind of new to Bluelight so hello every one! Wasn't sure whether to post in here but here it goes;
> Could you theoretically use methionine in the methylation process to change phenethylamine to methylphenethylamine (which i believe to be amphetamine?) or would you need another reagent such as iodomethyl, and also how would one go about doing this?
> I've been doing a lot of research on the internet about it and can't really find much about it other than a mention in PIHKAL, it just seems strange no-one has experimented with this.



the short answer is no. Methylating phenethylamine gives N-methyl phenethylamine, amphetamine is alpha methyl phenethylamine a completely different creature.
there is a longer answer but there is a no synthesis discussion policy on BL.


----------



## djsim

This sounds like a round-about synth question. I'll send this to Advanced DD... if they allow it you'll get better responses there as those guys are really on the ball with this kinda stuff


----------



## nuke

You can simply purchase 99% acetone.  It's pretty hygroscopic so it's generally hard to get it above 99.5%.


----------



## ebola?

If one were to inhibit her MAOB, would we expect the following analogy to hold in terms of effects:

amphetamine is to methamphetamine as phenethylamine is to n-methyl-phenethylamine?

And wouldn't a straight-forward methylating agent, as 'bean93' suggested, also yield n,n-di-methyl-phenethylamine, etc.?

ebola


----------



## bean93

oops I'm used to posting on another forum I'll be sure to read up on posting rules. Well thanks for the short answer pretty much all I needed. I take it N-methyl phenethylamine is unactive as theres not alot of material on it's research. Could anyone point me in the direction of a good biochem/pharmacology post they have read (Y)


----------



## ZzZzZ

After synthesis of JWH-018, what would a pure product look like? I've heard white is the purest, but a few vendors I've talked to have claimed to have the purest product around even if brown. For example, i just got this reply from a vendor:  "Its not white. and white dose not mean pure.
things like that have been chemcialy made that way. to look clean and often result in a weaker product. which can be cut with anything under the sun without visualy knowing. lots of white bulking powers etc.
i got lab results that the jwh  is 99.999 Assay even though its a brownish colour. "


----------



## vecktor

ZzZzZ said:


> 99.999 Assay even though its a brownish colour. "



thats bullshit for a start. 10 ppm total impurities, dont make me laugh.

A general point practically no organic chemicals except for special purposes like electronics are that pure.


----------



## hugo24

And no HPLC assay gives you 99.999% like results.But for sure,I can show you HPLC's showing a 100.000% pure Product ...

Altough you CAN color a product with ppm's of certain impurities.


----------



## Hammilton

Yeah, when you start going below 98.5% purity you start getting a little yellow.  I had stuff that was 96% pure that was pure yellow.

The only brown brown stuff I've seen was later found to be between 75 and 78% pure.  If you have brown stuff, it's probably between the 70s and 80s percent purity.  I've never seen JWH-018 that was in the 80-90% purity, though I'm sure someone here has.


----------



## nuke

Though colour isn't necessarily always an indicator of piss-poor product...  I had degraded 4-AcO-DET that went to a brown colour (assumably the n-acetylated version of 4-AcO-DET) but didn't encounter any major loss of the main product.


----------



## Hammilton

Right, absolutely, but in the case of JWH-018, pretty much all of the brown stuff around will be <90% pure.  It's possible that it could be higher, but it's rather unlikely.  The byproducts of 018 synth seem to be pretty strongly yellow.  I don't know what the brown shit is.

I know someone somewhere had commented on this, after doing extraction on the brown shit that was being passed around, but I don't remember what he said it turned out to be.

And the vendor is partially right, it would be possible for someone to cut the product so that it turned out to be white, but you'd end up with severely degraded product, in a way that ought to be obvious.

the claims that it's being "chemically turned white" - well, that's sort of true, but it's just basic extraction.  This is what the *no sources! - nuke* people were claiming when we were having our issues with them, and I believe that our issues cost them a lot of business, as they eventually changed labs and now have white product.

Most of these people are idiots and don't know better themselves.  I think they're probably buying the nonsense that their chinese labs are telling them.  It's obvious that these places have no problems faking the results.


----------



## dread

> It's obvious that these places have no problems faking the results.



Well yeah, just look at the recent 2cb-fly incident...


----------



## MeDieViL

*Does amphetamine interact with 5HT receptors?*

Does anyone know?


----------



## Swerlz

i dont think so.. I know meth as more serotonin activity than amp


----------



## nuke

It has a mild affinity for the serotonin transporter.  I don't believe it has any strong affinity for any of the serotonin receptors.


----------



## MeDieViL

Allright thank you, one more question.

What 5HT receptors decrease response to MDMA when antagonised? And are there any 5HT receptor agonists that decrease response to MDMA?

Thank you.


----------



## Bloodheart

*Dexedrine into Freebase Dextroamphetamine*

I'd like to start off by saying I read the rules and didn't think this question was against them, if so, I am sorry.  


My question is, has anyone extracted the dextroamphetamine dextroamphetamine sulfate from Dexedrine tablets and then turned it into freebase dextroamphetamine?  Does anyone happen to have a tek explaining the process?  Any help would be greatly appreciated.


----------



## chloral hydrate

I think the problem is that amphetamine is supposedly an oily ammonia like liquid when freebase so it would take some careful process to get it out. If you're trying to smoke it, you can maybe get away with amphetamine carbonate or bicarbonate which should decompose under heat to CO2, H2O, and freebase amphetamine.


----------



## Bloodheart

My goal would be to make some putty.


----------



## dread

Why?


----------



## ebola?

If everyone else lacks a copy of that one massive chart with various stimulants' binding affinities and propensities to release monoamines, I can load mine up.  Amphetamine is on there, I believe with double-digit affinities for DA and NA, and >1000 for 5ht.

ebola


----------



## chloral hydrate

You know I was probably wrong about the BP of amphetamine. On this thread it says BP is 203C of freebase. I couldn't find any MSDS on it. But by all means, try it.


----------



## MeDieViL

ebola? said:


> If everyone else lacks a copy of that one massive chart with various stimulants' binding affinities and propensities to release monoamines, I can load mine up.  Amphetamine is on there, I believe with double-digit affinities for DA and NA, and >1000 for 5ht.
> 
> ebola



Please upload it:D

I found this on wiki:


> 5HT2C receptors mediate the release of dopamine in response to many drugs,[6][7] including caffeine, nicotine, amphetamine, morphine, and many others.


Apperantly some serotonin receptors play a roll in amphetamines dopamine release.


----------



## Nibiru

The freebase might be caustic. Maybe dangerously so. Meth freebase is up around ph 8. I certainly would be careful.


----------



## nuke

Here you go:

http://en.wikipedia.org/wiki/User:Rocknroll714/affinities



> Apperantly some serotonin receptors play a roll in amphetamines dopamine release.


The study cited there refers to cocaine rather than amphetamine.



> Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence.
> 
> Bubar MJ, Cunningham KA.
> 
> Center for Addiction Research and the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
> 
> The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the "rewarding" effects of psychostimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2A R) and the 5-HT2C R. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2A R antagonists and/or 5-HT2C R agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2C R agonists may also effectively reduce cocaine intake in active cocaine users. At present, the progression of studies to probe the effectiveness of 5-HT2A R and 5-HT2C R ligands in the clinical setting is hindered by a lack of available selective 5-HT2A R antagonists or 5-HT2C R agonists for use in human cocaine abusers. However, a number of selective 5-HT2 R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.


----------



## Bloodheart

dread said:


> Why?



Who doesn't want to smoke amp putty?


----------



## nuke

You put it in an aqueous solution of sodium hydroxide and it precipitates out as an oil.  That's it.

Amph-H+ + Cl- + OH- + Na+ -> Amph + H2O + Cl- + Na+


----------



## dread

> Who doesn't want to smoke amp putty?



Who does?


----------



## Sturnam

1) Would a SSRI prevent the neurotoxicity from methamphetamine?

2) Is it safe to combine an NRI with a NE releasing agent?


----------



## permastoned

1) No

2) It is safe, but the NRI cancels out the effect of the NE releasing agent on the NE. Not that that really matters, because the effects of NE generally aren't that desirable.


----------



## nuke

The neurotoxic effect of fluoxetine coadministered with methamphetamine is weird,


> Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine.
> 
> Ricaurte GA, Fuller RW, Perry KW, Seiden LS, Schuster CR.
> 
> Repeated administration of large doses of d-methamphetamine produce long-lasting depletion of brain dopamine (DA) and serotonin (5-HT), as well as persistent decreases in the activity of their respective biosynthetic enzymes, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). The present results indicate that the inhibitor of 5-HT uptake fluoxetine, prevented the long-term depletion of 5-HT produced by large doses of methamphetamine (15 mg/kg X 5, 6 hr apart) in the neostriatum and hippocampus, while simultaneously augmenting the depletion of DA produced by this drug in the neostriatum. Fluoxetine also enhanced the prolonged neostriatal depletion of DA produced by a comparable regimen of d-amphetamine. In these doses (15 mg/kg X 5,6 hr apart), d-amphetamine did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus. Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine. This suggests that fluoxetine may inhibit the metabolism of amphetamines.





> 2) It is safe, but the NRI cancels out the effect of the NE releasing agent on the NE. Not that that really matters, because the effects of NE generally aren't that desirable.


They can be.  MDMA is selective for NE over DA and N-Ethylcathinone is reported to be a likeable stimulant.


----------



## ebola?

IIRC, MBDB hits NE rather prominently too, but not DA.  So there's a step in teasing neurology ------> phenomenology.

However...do we have selective enough dopamine or dopamine and serotonin releasers to show whether stimulant and empathogen "likeability" depends somehow on release of NE?

And as I recall, a particular selective NE releaser was widely found not to be fun (forgetting what it was).

We could conduct a similar exploration of reuptake inhibitors...but blocking SERT seems to do something very different from release.

ebola


----------



## permastoned

Farily selective NE releaser = pseudoephedrine


----------



## Eewanko

*???*

Hi i'm a newbie, i was wondering whether anybody out there can help, does anybody know, approximately, how many  studies have been done with beta- substituted 2- phenylethylamines? xx


----------



## nuke

d-Ephedrine or n-Ethylcathinone too.


----------



## Rogue Robot

we'll try ADD

HOMELESS -> ADD


----------



## Enkidu

ADD ---> Trash?


----------



## madsci

Just to clarify, as most of you probably know, serotonin decarboxylated to 5-hydroxytryptophan. Which is the active substance at the neurotransmitter sites. 
It is degraded by MAO in the presynaptic cleft, so basically any drug that inibits reuptake prolongs the effects of serotonin. 
As far as the specific receptors are concenened the most sedating one is the 5-HT 2a receptor, havent done enought experimenting / reading to fully understand the remainder of the receptors. 
An additonal interesting fact about 5-HT drugs is that there is an autoreceptor (research is currently being done on how this works) it takes about two weeks for these autoreceptors to desensitize which means more effect of the drug, unless of course, they target other classes of neurotransmitters such as catecholamines. Prescription meds tend to work on both.


----------



## ebola?

> Farily selective NE releaser = pseudoephedrine



I thought that ephedrine and pseudoephedrine also present significant direct agonism at adrenergic receptors.

ebola


----------



## permastoned

^My understanding, for pseudoephedrine at least, is that the direct affinity for NE receptors is quite weak/low. Ephedrine is different, it has significant direct agonist effects.However, to me it seems fairly irrelevant, as the overall action is still activation of the NE receptors. Ephedrine isn't that selective for NE however, it also releases some dopamine, and serotonin to a lesser extent.

Regarding n-Ethylcathinone, although this is a fairly selective NE releaser, it is metabolised to cathinone which has quite significant inhibition of dopamine reuptake.


----------



## chloral hydrate

I think aminorex is an interesting stimulant phenethylamine because of the absence of the a-methyl group that's necessary in phenethylamine vs. amphetamine but not in aminorex vs. 4-mar. Instead it has some cyclicized complex at b- and n- or whatever.

So EEwanko I think there could be some b-substituted phenethylamine that have strong central action, perhaps b-methoxy phenethylamine or something? I'm also interested.

And no nuke he wasn't asking about fucking amphetamines! he was clearly asking about b-substituted phenethylamines, not substituted anywhere but substituted at R-b.


----------



## Eewanko

lool, ok i relaise i jave to be really specific when questioning. thanks guys, n erm... just to clarify for future reference i am a she . so to rephrase, how many chenistry based studies have their been conducted on the synthesis of beta substituted phenylethylamines with both forms (d-Ephedrine  & n-Ethylcathinone ), and how successfully are their analogs detected by GCMS


----------



## nuke

chloral hydrate said:


> And no nuke he wasn't asking about fucking amphetamines! he was clearly asking about b-substituted phenethylamines, not substituted anywhere but substituted at R-b.



Those are selective NE releasers.  Sometimes things look wonky when merged.

Beta-substituted phenethylamines...  The cathinones are stimulants similar to amphetamines, the ephedrines are mostly active NE releasers/reuptake inhibitors, and the beta-ether compounds were problematic from a physical standpoint in PiHKAL.  I don't know much else about them.  They're fairly easily detectable by GC/MS, like most small compounds.


----------



## temuchin43

Hi guys, first post here - please be kind 

Is it possible that the CNS effect of oxymetazoline has been underestimated? Descriptions claim a negligible stimulating effect, and possible depression of CNS in children - but I've always felt a much more noticeable effect from this seamingly benign medicine.

It seems that whenever I use it I'm more choleric, assertive and overconfident - without it I'm more mellow, thoughtful and a bit indecisive.

And this is a "fair" comparison since I've spent 14 years of my life being addicted to this thing (2-3 times daily), with on and off periods. These effects are very consistent.

I'd appreciate your opinion on this


----------



## Sturnam

Can anyone find a source for wiki's claim that citicoline is a stimulant, or any studies of it being used in normal, healthy people?


----------



## Hammilton

nope.

on the matter or oxymetazoline- very unlikely.  It's similar to clonidine, I guess.

I would wonder if it had a plain phenyl ring instead of all that cabbage if it would be stimulating.  I suspect that it'll be too much like clonidine regardless, though.


----------



## temuchin43

Hammilton, thanks for your reply!

It confuses me a bit though - isn't Clonidine an a2 agonist? And Oxymetazoline mostly a1?


----------



## Artificial Emotion

^ Clonidine is in fact a direct-acting α2 adrenergic agonist.


----------



## Enkidu

Will someone please explain the pharmacological effects of a dopamine disinhibitor?


----------



## nuke

> Will someone please explain the pharmacological effects of a dopamine disinhibitor?



The antagonism of any downstream inhibitor of dopamine release, eg 5HT2C antagonism or 5HT1A agonism.  Mirtazapine being a good example.


----------



## bird^

*Quick question*

What program do you guys use to draw all of these molecules? Or do you just use MS Paint or something similar?


----------



## vecktor

chemdraw usually, however there are loads of free chemical drawing programs which are as good.


----------



## seep

I have Chemsketch, which is free but annoying as hell because it keeps telling me how much better it would be if I would purchase the parent program. I wish there were a biochem program where you could craft a molecule and administer it to an organism of your choice and have the program work out the effects viz binding sites and ADME kinetics.


----------



## Cloudy

I've never had a problem with chemsketch, though I haven't honestly used it much.

Anyway, I'm a chem major who currently in Organic I, just finishing up reactions of alkenes and alkynes, and I'm trying to start learning basic pharmacology, and my school doesn't seem to offer anything of the sort, with the exception of forensic toxicology (?).  I've found some good info (I haven't taken a full look yet, though) on MIT's open course website, but I'm curious as to if there are any sources that you guys recommend?

Thanks


----------



## Enkidu

nuke said:


> The antagonism of any downstream inhibitor of dopamine release, eg 5HT2C antagonism or 5HT1A agonism.  Mirtazapine being a good example.



Are those autoreceptors?


----------



## nuke

Enkidu said:


> Are those autoreceptors?



Well, probably not.  It depends on the neurons themselves.



> Serotonin Receptors
> 
> There is a paucity of information on the direct electrophysiological effects of serotonin on central DA neurons, and there is a similar lack of anatomical data suggesting the presence of serotonin receptors on DA neurons. There are over a dozen serotonin receptors (the rate at which new ones are cloned suggests that it is prudent not to specify an exact number), some of which are present only in certain species (see Serotonin Receptor Subtypes and Ligands). 5-HT2c (previously designated 5-HT1c) receptor transcripts are present in cells of the pars compacta, suggestive of colocalization in the A9 DA neurons. However, Chesselet and colleagues (19) have found that those pars compacta cells that express 5-HT2c mRNA are exclusively nondopaminergic.


http://www.acnp.org/g4/GN401000018/CH018.html

Check out this paper: http://www.jpp.krakow.pl/journal/archive/0608/pdf/229_0608_article.pdf

So it appears to be indirectly through GABA or glutamate or some other messenger.


----------



## enitpenima

1. What substances provide mental stimulation with minimal physical stimulation? Or alternatively, what can block the physical component of stimulants?

2. Why aren't substances like Bromantane more widely available?


----------



## boohigh

*Opiates and immune system.*

I have read that opiates suppress immune system. Do it means, that if  i get flu and will start to use codeine for easying symptoms it will prolong time of cure?


----------



## Giovanni

*Mephedrone in the freezer?*

Hi,

I was wondering what would be the best way to keep mephedrone (probably in a freezer I guess) and how long I could preserve it. Thanks in advance.

Greetings,

Gio


----------



## nuke

You could keep it out of the freezer and it'd probably be stable for an excessively long time.  The only instability is the secondary amine causing dimerization with the carbonyl function group, but it's probably very stable as a dry powder salt kept away from moisture.


----------



## Sturnam

Would an SNRI (desvenlafaxine) be contraindicated with o-desmethyltramadol? Since o-desmethyl lacks the serotonergic affinity that tramadol has, I'm thinking the combination would be safe, but I just wanna make sure.


----------



## nuke

I dunno, I would guess probably not.  I mean, I've taken DXM with SSRIs which is contraindicated but I'm still pretty alive.


----------



## rollnpeace

*Mephedrone*

Does anyone know how mephedrone works in the body? Like the actual chemistry of it.


----------



## Jack Jiggity Jaw

this dont belong in psychedelic check this thred out
http://www.bluelight.ru/vb/showthread.php?t=400517


----------



## Solipsis

Moved PD >> ADD


----------



## fluxy

*increase solubility of phenazepam the old way*

Is it possible to do this with some of the old was youd turn some brown into some number 4 shooting dope,



Ie:  citric acid?    raise the ph with a little Hcl?   

Apart from that,


Even though this is defenitely not H20 soluble,  Does that mean that one its in the body, and because of it highly liphphilic nature that it will reach the brain faster (think why Diaceytlmorphine reaches the brain).


I mean,  we can dissolve the shit in anything common enough,  but if you shake it up enough in a fit and then shoot away,  It should produce some prety immediately noticeable effects right????? (i know iknow, pay attention to measurements,  carefully,  but this is not eyebealling.)   Im just worried that people are going to do this anway,  and in the intersts of harm reduction what is the relevent info that should be spreaded about this practice.  

  It seems some people just have to shoot everything.....


----------



## negrogesic

If you wanted you could make a solution similar to the lorazepam injectable. Phenazepam is similar in structure to lorazepam and probably has similar pharmacology/dynamics, but with different pharmacokinetics...

In other words you would want PEG400-propylene glycol with a preservative like BnOH. This solution would need to be micron filtered. 

Do not inject powders not in solution. This is how you lose limbs...


----------



## nuke

rollnpeace said:


> Does anyone know how mephedrone works in the body? Like the actual chemistry of it.



It is thought and highly likely that it releases serotonin, norepinephrine and dopamine, similar to methamphetamine.


----------



## mmodred123

*Codeine ceiling*

Wikipedia, in its article on codeine, flatly denies that there is a codeine ceiling effect. Who is right? Why?


----------



## nuke

Wikipedia is full of itself and there is indeed probably a ceiling effect for codeine:



> Psychopharmacology (Berl). 1998 Nov;140(2):191-201.
> Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers.
> Walker DJ, Zacny JP.
> 
> Department of Anesthesia and Critical Care, University of Chicago, IL 60637, USA. dwalker@dacc.uchicago.edu
> The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included to test this assumption. Codeine and morphine increased ratings of "feel drug effect" but had little effect on other subjective measures, including the Addiction Research Center Inventory, visual analog scales, and adjective checklists. *The few subjective effects that were observed were modest and were dose-related for morphine but not for codeine*. The drugs did not affect performance on Maddox-Wing, digit-symbol substitution, coordination, auditory reaction, reasoning, and memory tests. *Dose-related decreases in pupil size (miosis) were observed following codeine and morphine. Ratings of pain intensity decreased in a dose-related manner for morphine but not for codeine.* Plasma codeine and morphine levels varied as an orderly function of dose. These results suggest that oral codeine and morphine are appropriate drugs for outpatient pain relief because they are effective analgesics at doses that have only modest effects on mood, produce few side effects, and do not impair performance. *The results also suggest a possible ceiling effect of codeine on analgesia and subjective effects.*



http://www.ncbi.nlm.nih.gov/pubmed/9860110

My guess is that it is related to it's need to be metabolized into morphine by another P450 enzyme or to C-6-G.  Codeine-6-glucuronide is another active metabolite that provides mu-opioid agonistic effects.


----------



## Sturnam

Cloudy said:


> I've never had a problem with chemsketch, though I haven't honestly used it much.
> 
> Anyway, I'm a chem major who currently in Organic I, just finishing up reactions of alkenes and alkynes, and I'm trying to start learning basic pharmacology, and my school doesn't seem to offer anything of the sort, with the exception of forensic toxicology (?).  I've found some good info (I haven't taken a full look yet, though) on MIT's open course website, but I'm curious as to if there are any sources that you guys recommend?
> 
> Thanks



Find books on pharmacology. Both e-books and real books are good. Depends which area of pharmacology you're interested in really. Looking through journals helps, and your school will probably have access to pretty much all of them. Some basic neuroscience helps. Also, try independent study. Email a professor and say you'd like to work with them.


----------



## yaesutom

*reuptake inhibitors vs releasing agents*

Do stimulants that are mainly reuptake inhibitors feel subjectively different to ones that work mainly by acting as a releaser, feel different for that reason?  

I guess what i'm trying to ask is, since I love d-amphetamine & d-meth (and even BZP), and similar stimulants, but I find methylphenidate / desoxypiperadol / MDPV etc kind of shitty.. is it because of them acting as releasers vs uptake inhibitors?  Or is it something else like the ratio of effects on DA/NE/SERT..

It just seems that the releasers i've tried work WAY better, feel better in some way that the DA reuptake inhibitors i've tried severely lack.


----------



## nuke

The releasers usually cause greater levels of monoamine release than the reuptake inhibitors.  Though d-AMP and METH also have about even levels of DA/NE release, whereas the only reuptake inhibitors on the market that do are dextromethylphenidate and cocaine.  Regular old methylphenidate I can barely even feel for some reason, and it has a much higher affinity for NE than DA.  Same with MDPV, most likely.

DA/NE reuptake inhibitors are most of the time selective for NE over DA, probably just for the reason of the NET being more promiscuous.


----------



## yaesutom

> The releasers usually cause greater levels of monoamine release than the reuptake inhibitors. Though d-AMP and METH also have about even levels of DA/NE release, whereas the only reuptake inhibitors on the market that do are dextromethylphenidate and cocaine. Regular old methylphenidate I can barely even feel for some reason, and it has a much higher affinity for NE than DA. Same with MDPV, most likely.
> 
> DA/NE reuptake inhibitors are most of the time selective for NE over DA, probably just for the reason of the NET being more promiscuous.



Ahh.. thanks for that info.  Amphetamines are really calm and relaxed.. mephedrone is also (but prob from the serotonin), MDPV and methylphenidate cause too much "sketchyness" and anxiety.   I wish there was a real good cheap research chem stimulant that was as relaxed as amphetamine.


----------



## hamhurricane

quick question: im researching the history of methylphenidate and i cannot find info about where it was initially synthesized, and who was responsible (although im pretty certain it was in italy as the first paper on its synthesis is in italian) anyone know a bit about its genesis, aside that it was marked by ciba etc?


----------



## MurphyClox

Methylphenidat was synthesized for the first time im 1944 by Leandro Panizzon (indeed italian) at Ciba (now Novartis; based in Basel, Switzerland; so it's practically a swiss invention, not a italian one). The tradename "Ritalin" is said to be derived from his wife's name Marguerite ("Rita").

- _Murphy_


----------



## nuke

Richard L. Myers, in "The 100 most important chemical compounds: a reference guide", states that it was named after his wife because she was the one who did the first human bioassays of the compound and found it be a stimulant.  She had low blood pressure, so the compound treated the condition and she would often take it before tennis.  The original name was "Ritaline" instead of the abbreviated "Ritalin".  Quite a story!

The original synthesis starts with 2-Cl-pyridine and Benzyl cyanide.  I won't detail the rest, but you should be able to figure it out!


----------



## ebola?

This isn't remotely advanced, but I don't think I'll get good info in OD:
what can I do with GABA powder?  My original plan turned out to be a tad beyond my means (*cough*).

If I were to take some GABA, would it potentiate a GABA agonist active in the CNS by displacing the drug from somatic receptors, making said drug more likely to end up in the brain?


----------



## lyrrad85z

concerta gels up when i try to bang it. i end up just eating the goo, but i know how good it feels to shoot a ritalin... how do i cook it down?


----------



## dread

> concerta gels up when i try to bang it. i end up just eating the goo, but i know how good it feels to shoot a ritalin... how do i cook it down?



You don't shoot concertas. They'll destroy your veins.


----------



## N0 W4RN1NG

yaesutom said:


> Ahh.. thanks for that info.  Amphetamines are really calm and relaxed.. mephedrone is also (but prob from the serotonin), MDPV and methylphenidate cause too much "sketchyness" and anxiety.   I wish there was a real good cheap research chem stimulant that was as relaxed as amphetamine.



http://en.wikipedia.org/wiki/1-Phenyl-2-methylaminobutan-1-one

It's out in the wild right now, and the feedback suggests it's a very vanilla 'd-amp feeling' stimulant, which is exactly what you (and I) are looking for.



ebola? said:


> This isn't remotely advanced, but I don't think I'll get good info in OD:
> what can I do with GABA powder?  My original plan turned out to be a tad beyond my means (*cough*).
> 
> If I were to take some GABA, would it potentiate a GABA agonist active in the CNS by displacing the drug from somatic receptors, making said drug more likely to end up in the brain?



I can't answer your last question, although it's an interesting idea. As to what to do with all that GABA...sandmeyer!


----------



## ebola?

I'm a sociologist.  Like I said, beyond my means.


----------



## N0 W4RN1NG

ebola? said:


> I'm a sociologist.  Like I said, beyond my means.



Dude, I'm certainly no chemist, I'm a 20 year old psych major, if I can pull it off anyone can haha. 

Just out of curiosity, it's not the BN GABA, is it? I've heard from a few sources now that that powder is too impure to be used as a precursor...


----------



## ebola?

We can't really talk about this

The short of it is, I lack the knowledge and equipment to reliably extract the product.  I would also never manufacture a scheduled compound.

And it is not that brand.


----------



## dread

alexson said:


> New question: What kind of idiot first claimed JWH is supercarcinogenic? Napthol/Napthalene/their burning products are on the same level of carcinogenicity as Benzene and it's friends. And people have been smoking phenyl compounds for how long? Napthalenoyl or whatever is not an epoxide super-carcinogen as some paranoid people might have you to believe.



What kind of idiot refuses to accept the facts?

http://www.bluelight.ru/vb/showthread.php?t=474536


----------



## StrawPipes

I have a funny question.  How do you guys know so much about this shit?  I thought I had a good understanding of Neuroscience but it's nothing compared to some people here.

After I take General Chem 1+ 2, Organic chem 1 + 2, and Biochem, will that get me a little caught up some of the people here in ADD?


----------



## hamhurricane

i have a question about the metabolism of lys-amp, i understand that the lysine is cleaved by trypsin enzymes but why does this result in the delayed onset of the drug? is it that there is not enough trypsin to do the conversion all at once, so that some of the lys-amp is effectively 'waiting' while the rest is being converted? 

this makes me wonder about the potential of lys-PEA which could (at the very least) take care of the need for constant redosing, and since (short) duration is correlated with habituation perhaps this could lessen the abuse potential of the drug.


----------



## nuke

StrawPipes said:


> I have a funny question.  How do you guys know so much about this shit?  I thought I had a good understanding of Neuroscience but it's nothing compared to some people here.
> 
> After I take General Chem 1+ 2, Organic chem 1 + 2, and Biochem, will that get me a little caught up some of the people here in ADD?



Well, it'll help.  Most students just ingest stuff as quickly as possible to try to regurgitate it on exams and then forget about it.  Unfortunately a bunch of the theory is kind of useless anyway, compared to actual lab experience.  There are probably lots of texts at your university library to look into if you are bored and want to get ahead.


----------



## nuke

hamhurricane said:


> i have a question about the metabolism of lys-amp, i understand that the lysine is cleaved by trypsin enzymes but why does this result in the delayed onset of the drug? is it that there is not enough trypsin to do the conversion all at once, so that some of the lys-amp is effectively 'waiting' while the rest is being converted?
> 
> this makes me wonder about the potential of lys-PEA which could (at the very least) take care of the need for constant redosing, and since (short) duration is correlated with habituation perhaps this could lessen the abuse potential of the drug.



The acylation step of catalysis is rate limiting in trypsin, so probably the substrate saturates the available enzymes and the remaining lysdexamphetamine has to wait for substrate pocket availability.


----------



## ebola?

ham hurricane said:
			
		

> lys-pea



whoa...great idea!   Any chance of accidental overdose via rapid metabolism though?

ebola


----------



## N0 W4RN1NG

alexson said:


> Nope, trypsin is found in digestive system, and assuming you bypassed MAO in digestive system, it still wouldn't be more effective then let's say injected PEA.



Right. But lis-dexamp, especially in high doses, releases d-amp *LONG* after 3-4 hours in (one time I took close to 300mg and I was feeling rushes like 9 hours in), which means that at least a significant portion of lis-dexamp is making it into the bloodstream.


lis-PEA would probably not be degraded by MAO, and although a fair bit would probably be destroyed in the stomach, once you initially clog the trypsin enzymes you'd probably be able to absorb all that lis-PEA into your blood stream for a slow and steady release...

I think it's a great idea.


----------



## Cloudy

What databases and journals do you guys use for drug chemistry, pharmacology, etc?  I'm getting more and more into pharmacology and drug chemistry, and I've realized once again that I have access via my university to many different resources.  One in particular I know is useful is pubmed, which I do have access to.  What others do you guys recommend?


----------



## N0 W4RN1NG

alexson said:


> Excellent point, but are you suggesting that lis-PEA itself is active, and not just the metabolite PEA? Because as soon as Lis-PEA is turned to PEA, it would be very prone to oxidation anywhere (even in the blood stream) by MAO-B which is present in blood cells and in the brain, if lis-PEA can even cross BBB. Injected into the blood stream, PEA is found ineffective (in Pihkal).



I am not suggesting that lis-PEA is active, especially since lis-dexamp isn't.

However, PEA is active even when taken orally. It is well documented that people can take 2-3g of PEA straight up and get a pretty intense 10 minute rush. Since MAO is more concentrated in the GI tract than in the blood, I would assume that if you could sneak the PEA past your stomach you would get, at the very least, better effects than you would orally.

Taking several grams of lis-PEA would, in fact, be very similar to having a PEA IV drip.

(someone correct me if I'm wrong here)


----------



## ebola?

> Excellent point, but are you suggesting that lis-PEA itself is active, and not just the metabolite PEA? Because as soon as Lis-PEA is turned to PEA, it would be very prone to oxidation anywhere (even in the blood stream) by MAO-B



Some of us have destroyed our endogenous MAOB.


----------



## hamhurricane

without getting into specifics would lys PEA be something one could synth from PEA? i have always had the impression that binding lysene to a given molecule was difficult because the only RC i have seen with such a structure is lys-MDA.


----------



## dread

Is an amide of pyrrolidine called a "pyramid?"


----------



## vecktor

hamhurricane said:


> without getting into specifics would lys PEA be something one could synth from PEA? i have always had the impression that binding lysene to a given molecule was difficult because the only RC i have seen with such a structure is lys-MDA.



very easy.

the reason as far as I can see that lys RC's are not more commonplace is that like in the case of Lys-MDA the highly illegal amine is required for synthesis.


----------



## ebola?

yes, and an unreacted intermediate would render the whole endeavor moot, here.

ebola


----------



## zero zero

*why not these phenylethylamines*

*2,3-methylenedioxy 4-methoxy 5,6-methylenedioxy phenylethylamine

2,5-methoxy 3,4-methylenedioxy phenylethylamine

2,3-methylenedioxy 4,5-methylenedioxy phenylethylamine*

I found 2,5-methoxy 3,4-methylenedioxy amphetamine in Shulgin.



> (with 75 mg) This was equal to somewhere between 75 and 100 micrograms of LSD. I was caught up with the imagery, and there was an overriding religious aspect to the day. The experience had an esthetic value. I liked it.



I wonder why he didnt try a mescaline like dose.


----------



## nuke

Probably because the phenethylamines with a 3,4-dimethoxy group are so readily metabolized, or maybe the chemistry is hard.

You're welcome to make them yourself and taste them.  I mean, the synthesis for the 2 carbon analogue of DMMDA is right there in PiHKAL if you just change one chemical.


----------



## zero zero

So are they hard to synth or not

Mescaline is not too easily metabolized and I dont think 3-methoxy 4,5-methylenedioxy phenylethylamine is.


----------



## nuke

I just gave you the one synthesis.

Lophophine and mescaline are both fairly easily metabolized, which is why the large doses are necessary for their activity (if lophophine is indeed even active).  Mescaline probably requires such a high dose to saturate whatever enzyme degrades it.


----------



## ebola?

There were numerous bioassays that Shulgin didn't get to because he was working on something more promising at the same time.


----------



## zero zero

I guess that they were too hard for him to make. I think that you have to find an essential oil with the same substitution pattern on the benzene ring?


----------



## Hammilton

We can say quite certainly that he didn't leave something out because they were too much work.

1.  You start including much more and just the PEAs need to come out in a multi volume collection.

2.  Many just aren't that interesting.  The difference between the amphetamines and the PEAs is notable, but we're talking degrees of difference, not worlds.

3.  Mescaline is definitely easily metabolised.  You don't need 2-500mg to get a dose just because it's not very potent.  If it weren't the TMAs would be really weak too.


----------



## bad news

Methyl-1-Etiocholenolol-Epietiocholanolone
can anyone break this down for me  I have no chem back ground

Thanks 
Bad News


----------



## ebola?

I forget if I asked in this venue, but why might propylhexedrine have visuals for some people (above and beyond visuals induced by straightforward amphetamines, for those susceptible)?

There appears to have been no research on receptor-affinities...well, obvious adrenergic agonism is there. . .  The cyclohexane ring would be wacky enough to preclude 5ht2a agonism, right?

ebola


----------



## dread

> 2,5-dimethoxy 4-something N-desmethyl propylhexedrine?



Won't work, aromatic ring is required for 5ht2a binding.



> Offtopic, does anyone know if either 4-chloro phenethylamine or 3,4-dichloro phenethylamine is active?



No idea. Could be, but the 4-chloro might be neurotoxic.


----------



## Sturnam

Some of my friends that use heroin say that when smoking off aluminum foil, you must:
A) use the dull side to smoke off of, because the shiny side has chemicals on it,
and
B) you must "preheat" the shiny side to burn off the chemicals

I'm 99% sure this is just junky folklore, but does anyone know if commercially produced aluminum foil might have any added chemicals that might be harmful when vaporized? I know the aluminum itself doesn't pose any threat, but maybe they coat it with something that is harmful?


----------



## dread

No, regular foil has no such chemicals.

Foils from cigarette boxes, candy bars and such might have, though.


----------



## FlowerOfLife

shibireru said:


> What are some readily obtainable substances which can produce death quickly, painlessly, and reliably?
> 
> Difficulty: No helium, carbon monoxide, nitrogen, nitrous oxide, or other inert gas.
> 
> P.S.  I recently discovered that the handgun that I was planning to use if ever my hope should be exhausted was locked up.  The cathartic feeling of safety and control that it produced to know that I could use that gun to kill myself is now gone and I'm feeling claustrophobic.  I don't plan on killing myself right now, I just want these feelings of fear and worry over what travails the future has in store for me to abate; there's nothing worse than being trapped / cornered / helpless / stuck between a rock and a hard place.



Watched a documentary once about LSD, think it was The Beyond Within (could be wrong) and the guy had cancer or something at the end and he had his wife IV 200mg of LSD into him in 2 doses to end himself, always figured that would be a good way to go if need be 8)


----------



## Hammilton

dread said:


> Won't work, aromatic ring is required for 5ht2a binding.





I don't know about that.  Best I can tell, they've never been studied for 5HT2a affinity.  Would like to know for sure, though.


----------



## hamhurricane

dread said:


> No idea. Could be, but the 4-chloro might be neurotoxic.



4-Cl-phenylalanine is used experimentally as a "a specific depletor of serotonin levels"

i would not go anywhere near 4-Cl-PEA


----------



## Hammilton

Yeah, excepting F, the 4-halo PEA's aren't good (and excepting 2,5 and probably 3,5 dimethoxy.  lots of other substitutions that may or may not be safe, but it's an area that I'd be wary about).

Actually, I would like to see 4-fluoro phenethylamine. It probably wouldn't be active without an MAOI, I liked 4-FA, so maybe this would be good.


----------



## dread

I'm kinda interested in 3-methoxy-4-chloro-amphetamine, and why not the PEA as well... anyone know if it's ever been assayed?


----------



## optimum000

*knowledge is power*

Hey for all those people who are VERY knowledgable in the field of basic pharmacology and advanced pharm.......could you please shed some light on acronyms and the theory of both basic and advanced for I want to become a pharmacist down the road and already have a basic knowledge for chem and pharmacology.......I know its kind of broad...but I guess what I am asking is what drugs do what for what and how drugs help people in the big scheme...how they are absorbed distributed, metabolized, and excreted.


----------



## Rectify

Is 3,5-dimethoxyamphetamine active?


----------



## seep

optimum000 said:


> Hey for all those people who are VERY knowledgable in the field of basic pharmacology and advanced pharm.......could you please shed some light on acronyms and the theory of both basic and advanced for I want to become a pharmacist down the road and already have a basic knowledge for chem and pharmacology.......I know its kind of broad...but I guess what I am asking is what drugs do what for what and how drugs help people in the big scheme...how they are absorbed distributed, metabolized, and excreted.



You may like The Color Atlas of Pharmacology. The torrent is widely available.


----------



## hamhurricane

im sure most of you are familiar with the ORAC scale, i only see it used to evaluate the antioxidant activity of different fruits, vegetables, legumes etc. does anyone know of an ORAC chart with a comparison of the common pharmaceutical antioxidants like ALA, COQ10, idebanone, n-acetyl-carnatine, n-acetyl-cystine etc?
many of them are referred to as "potent antioxidants" but i would like a way to objectively compare their strength relative to one another and to various fruits...


----------



## seep

hamhurricane said:


> im sure most of you are familiar with the ORAC scale, i only see it used to evaluate the antioxidant activity of different fruits, vegetables, legumes etc. does anyone know of an ORAC chart with a comparison of the common pharmaceutical antioxidants like ALA, COQ10, idebanone, n-acetyl-carnatine, n-acetyl-cystine etc?
> many of them are referred to as "potent antioxidants" but i would like a way to objectively compare their strength relative to one another and to various fruits...



I'd look in one of the forums of the IMMORTALITY INSTITUTE (although a half hour lurking there may make you wish for death).


----------



## vortex30

seep said:


> You may like The Color Atlas of Pharmacology. The torrent is widely available.



Dude, thanks for the recommendation, this is a great book! :D

EDIT

Oh yes, I got a quick question. Would 4-AcO-DMT fumarate be soluble in water? I use liquid titration to get mostly accurate doses of RCs with this dose range as I only have a 0.01g scale (usually dissolve 100mg in 10ml water so 1ml = ~10mg), but am wondering if this will be a viable method with 4-AcO-DMT?


----------



## hamhurricane

^^^
yes its soluble

here is a question which is obviously hard to answer but i would appreciate any help. does anyone have a rough idea of how the profits of the black/grey market drug economy compare to that of mainstream pharmaceutical companies? more specifically how MDMA sales compare to those of something like prozac or another common SSRI?


----------



## Hammilton

Rectify said:


> Is 3,5-dimethoxyamphetamine active?



Who knows.  4-bromo-3,5-DMA isn't exactly a winner.


----------



## crakkbakk

*What is the Binding Affinity Ratio (Ki) of THC to CB1:CB2?*

I googled this but there are too many other conflicting searches with topics on similar terms.  Does anyone happen to know or have a link handy that shows the Ki of THC's binding affinity of CB1:CB2?

I want to find a cannabinoid analog with as close as possible of a ratio of CB1:CB2 to THC. My theory is that it will provide the most similar experience as THC.

JWH-018, for example, has a Ki of 0.3:1 CB1:CB2

I love JWH-018, when I was on probation I smoked it every single day and did wonders, but of course nothing can compare to marijuana.  My theory is that finding a cannabinoid with a similar ratio will be more suitable.


----------



## nuke

delta 9-THC CB1 7.1 nM (JPET August 1996 vol. 278 no. 2 871-878)

delta 9-THC CB1 54nM (Annu. Rev. Pharmacol. Toxicol. 1998. 38:179–200)
delta 9-THC CB2 76nM (Same as above)


----------



## dread

Although, cannabis is not only THC. Shouldn't you calculate the average values of CBD and THC, then find a synthetic cannabinoid with affinities close to that?


----------



## SquizzyBase

*suboxone question?*

so here goes. im addicted to oxycodone have been for almost a year now. and for the past 4 months i plug my dose only. well the other day i thought id try an oral dose of half my plugging dose and i got blasted high. whoa sick. so i dont think anything of it except that maybe i just forgot what it feels like to take oral oxy. fast forward to today. im taking some sub to hold me over till i can get some more oxy. and as i plug my dose i get a slight buzz. and poof i remember reading in a "subplug" thread someone saying that the less bupe u take maybe the more norbupe can be recievd in ur mu receptors. well assuming that this is possible could it be possible if one wer inclined to get high off bupe to take a bupe dose orally which although has very low ba for bupe. the passs of 1st and 2nd metabolism would cause much more bupe to be converted to norbupe which would flood the brain since so little bupe would get thru???


----------



## Hammilton

you'd have to significantly increase your dose, and you'd end up wasting lots of bupe.

better alternatives, but those who've tried them agree, they're generally pointless too.


----------



## Solipsis

How come PEA's like 2C-B resemble dopamine chemically but work as 5-HT agonists? Wouldn't you expect something like DA agonism (though I've never even heard of that)?


----------



## dread

It could be. Otoh, steric hindrance...


----------



## Rectify

Yes, 2,5-dimethyl-3,4-MDA *probably* is active, but there is some amount of pure speculation in predicting the properties of any drug before it has been tested.

Also, when you say, "2-methyl-MDA," I presume you mean 2-methyl-3,4-MDA and not 2-methyl-4,5-MDA, which is inactive.  (The numbering of the ring gets prioritized to the closest substituent to the alkyl chain therefore making clarification necessary in such instances.)


----------



## dread

My understanding is that the methoxy groups on the aromatic cycle give them 5ht affinity, being in correct positions for hydrogen bonding with the 5ht receptor. But I may be wrong about that, lately I seem to be wrong about lots of things...


----------



## nuke

Solipsis said:


> How come PEA's like 2C-B resemble dopamine chemically but work as 5-HT agonists? Wouldn't you expect something like DA agonism (though I've never even heard of that)?



It's because of the substitutions on the aryl ring (phenyl ring).  The ring makes for a planar configuration which is necessary for being a substrate for many receptors, while the ethers on the ring appear to provide hydrogen bonding for something inside the 5HT2A/C receptors that allows them to be agonists while also preventing their metabolism.  The amine tail, normally associated with dopamine, appears to configure itself to interact as the amine tail of tryptamine does, probably hydrogen bonding with something acidic in 5HT2A/C receptors.  It's thought that the orientation of the phenethylamines inside the receptors is slightly different than tryptamines on a 3D plane too.  The basic answer is that all the substitutions cause it to have a very different shape and hydrogen bond capable structure that fits more "key-like" into the 5HT2A/C receptors than into the D1-D4 receptors.


----------



## (zonk)

2,5-dmo-3,4-mda has been made and tested, it's like another DOM analog but less potent. MDA is slightly trippy and a serotonin releaser, adding anything at the 2 and/or 5 positions is just going to make it a straight hallucinogen and not so much a serotogenic stimulant. Maybe at the 2 position it can take some sort of substitution without being too psychedelic but it's iffy.


----------



## Giovanni

*How stable are these compounds?*

I ask this question about a lot of drugs, but I'm no chemist and I like to know how long I could keep this stored... So how stable are 2C-X's and could there be a difference between various 2C-X's. How long could I keep it stored? The same question for etaqualone. Any extra info on etaqualone is also welcome. Thanks in advance.

Kind regards,

Gio


----------



## shulgin_jr

2cx compounds will be very stable as long as they are being stored as the hydrochloride/hydrobromide etc. salt.  If your material is a solid powder, then it is going to be a salt, since most if not all the 2cx compounds I'm aware of are oils in the freebase state.

For compounds like 2cb, and 2ci you should keep them stored in a dark place.  The carbon halide bonds in these materials are relatively strong (because the iodine/bromine are on the aromatic ring) but leaving them out in the sun for a prolonged period of time would not be advisable.  

The other 2cx compounds with no halogens would probably be more stable by my guess.

If you wanted to store them for 10+ years, you could get a ziplock freezer bag with a good seal and a couple of those little pouches of sillica gel you find in OTC pill bottles to keep the 2cx's dry (taking them in/out of the freezer often will build up moisture and make them soggy/sticky).  

If you keep them in a cool dark place, they will last a long time.


----------



## Coolio

I've yet to see a 2C* degrade under poor conditions.


----------



## dread

*Fencamfamine mechanism*

When they say that Fencamfamine is a partial DA releaser and a partial DRI, how exactly does that work? Does it reverse some DAT:s and inhibit others? Or does it bind to the DAT and then only reverse it occasionally? Or is there some completely different mechanism?

Wiki says it releases DA by the same mechanism as amphetamine, but does not say what mechanism it uses to inhibit the reuptake.


----------



## seep

Does anyone have pharmacokinetic data for MDOH?


----------



## shienar

Hello

Please identify this random substance. I have a non-saturated HPLC trace for you to look at. Its run on Acetonitrile / Water + 0.01% Trifluoroacetic acid. Told its Valium please confirm. 





Thank you i can provide more info if needed. I need a response by friday if you would be so kind.


----------



## vecktor

^you can't confirm id just with UV and a HPLC retention time unless either

you ran the HPLC conditions, flow, gradient, column which are the same as it has been listed somewhere else there are plenty of HPLC refs for ID of benzodiazepines, you would also have to run either an internal standard in your sample or a separate standard because of dead volume etc in the machine
or 
Unless you have a reference sample to run under the same conditions the id by retention time would be possible.

A quick look shows there are also two materials here one eluting later but partially co-eluting with the major peak. 

MS would be better.

V


----------



## Solipsis

Thanks by the way Nuke


----------



## ebola?

I suck at running searches: has it ACTUALLY been confirmed that k2 smoke blend is jwh18 + jwh73?


----------



## Captain.Heroin

*temazepam metabolization*

I have a question for the pharmacology buffs (you all know who you are ) - why is it that cimetidine and/or WGFJ work on most benzodiazepines, but not temazepam?  

How is temazepam metabolized?  Why are its metabolites inactive?  

Is there a way to prevent temazepam from being metabolized as quickly as it normally is?  

Thank you in advance.  I remember reading on wiki that temazepam isn't boosted by cimetidine or WGFJ at all.


----------



## drug_mentor

Hey guys, I am an avid codeine user and have wondered something for a while. I know CYP2D6 inhibitors slow down the metabolism of codeine and while reducing the strength of a dose also increase the duration. Codeine has a 'ceiling dose' of 400-500mg.

What I wondered is if you could inhibit CYP2D6 to a reasonable level and then take 800-1000mg of codeine and achieve peak effects from the ceiling dose but with twice the standard duration? I love my codeine but it just doesn't last long enough, this idea seems like it could work to me but I am nowhere near as knowledgable as the posters over here in ADD.

If anybody could shed some light on this I would appreciate it very much.  Thanks!


----------



## monstanoodle

Captain.Heroin said:


> I have a question for the pharmacology buffs (you all know who you are ) - why is it that cimetidine and/or WGFJ work on most benzodiazepines, but not temazepam?
> 
> How is temazepam metabolized?  Why are its metabolites inactive?
> 
> Is there a way to prevent temazepam from being metabolized as quickly as it normally is?
> 
> Thank you in advance.  I remember reading on wiki that temazepam isn't boosted by cimetidine or WGFJ at all.



It's metabolized by conjugation and demethylation. One metabolite, N-desmethyl temazepam, is only present in small quantities (7% I've read).
Not sure if they're inactive or not though I'm afraid


----------



## Captain.Heroin

monstanoodle said:


> It's metabolized by conjugation and demethylation. One metabolite, N-desmethyl temazepam, is only present in small quantities (7% I've read).
> Not sure if they're inactive or not though I'm afraid



I see, thank you for the info!  If anyone else has anything to add that would also be appreciated.


----------



## monstanoodle

Yer quite welcome  I've had a good look but haven't found much info at all which is silly. It's been around since the late 60's and has been in use since then.
You'd imagine there'd be extensive research into such things


----------



## dread

N-desmethyl-temazepam is the same as oxazepam and is not inactive, although very weak in effects.


----------



## seep

monstanoodle said:


> Yer quite welcome  I've had a good look but haven't found much info at all which is silly. It's been around since the late 60's and has been in use since then.
> You'd imagine there'd be extensive research into such things



There is.

CYP3A4 generally does 2 things to this family of benzos: it N-demethyates them and it 3-hydroxylyzes them.

Here are temazepam (L) and oxazepam (R): 





 , 
	

	
	
		
		

		
		
	


	




Oxazepam is N-desmethyl temazepam (the 7% metabolite you mentioned).

As you can see, they both have an -OH on the 3 carbon. This -OH means there's very little for CYP3A4 to do. The body then kicks enzymes called glucuronyl transferases into action so that the -OH becomes -O-glucuronide (basically it replaces the H with a glucose unit, unless I'm botching the stereochemistry). This latter product is definitely inactive and eventually pissed away.

*Extending the duration of temazepam:* I'm guessing there are 2 possible routes:

1) Induce CYP3A4. This is possibly going to weaken the experience, but it's worth a try.
2) Inhibit glucuronidation. There's a thread on this somewhere. Search ADD for NAPROXEN STATIN (I think that'll get you tthere).


----------



## seep

Are both enantiomers of temazepam equally active does anyone know?


----------



## dread

seep said:


> Are both enantiomers of temazepam equally active does anyone know?



No idea. However I _think_ the one used in pharmaceuticals is the one where the bond to the OH goes downward from the diazepine ring if the molecule is looked at as in the above post (cba to figure out if it's R or S)


----------



## seep

According to chemspider it's racemic. This is the correct drawing:






For R, the -OH projects out of the page.


----------



## seep

seep said:


> 2) Inhibit glucuronidation. There's a thread on this somewhere. Search ADD for NAPROXEN STATIN (I think that'll get you tthere).



Apparently the search engine discriminates between singular and plural. This is the thread.


----------



## surrеalist

This thread is spectacular in comparing the structures of psychedelics- mainly showing that the 5-methoxy group on psychedelic phenethylamines is analogous to the indole nitrogen, and the 2-methoxy is analogous to the 5-hydroxy in serotonin, and how it all fits into LSD.





The figure above shows psilocin. If one were to create the phenethylamine analogue of psilocin, it wouldn't be BOD and it shouldn't even be a phenethylamine. Here is what it should be:





I get the feeling that if somebody actually made this compound, it would be either a complete success or a complete failure (no activity). But then again, who knows.


----------



## Enkidu

AFAIK, f&b's original assertion is incorrect. Here's something for your viewing pleasure.

http://en.wikipedia.org/wiki/ORG-37,684


----------



## surrеalist

Yeah, that is definitely similar, except the non-methoxy ether in ORG doesn't overlay over the 4-hydroxy in psilocin (and the ORG methoxy ether isn't overlaying the 4-hydroxy, it's overlaying the nitrogen in the indole part of psilocin). Yet now I am even more certain that the compound I suggested is active.

But it's interesting, thanks. What exactly was F&B most incorrect about?


----------



## any major dude

Does anyone know of where I can find some images of fMRI, PET, SPECT or similar scans of people on serotonergic psychedelics?  Any help would be greatly appreciated.  Been trying to use google images, but no real luck.  For some reason, regardless of what else I type in, anything with LSD gets mostly results that are of blotter paper & hippies


----------



## dread

> But it's interesting, thanks. What exactly was F&B most incorrect about?



one quote answers another...



			
				Hammilton said:
			
		

> Tryptamines and Phenethylamines do not bind the same way. When it comes to 5HT2a binding, it's a mistake to look for homologous positions, because they're not interacting with the receptor in the same way.


----------



## Enkidu

surrеalist;8049027 said:
			
		

> Yeah, that is definitely similar, except the non-methoxy ether in ORG doesn't overlay over the 4-hydroxy in psilocin (and the ORG methoxy ether isn't overlaying the 4-hydroxy, it's overlaying the nitrogen in the indole part of psilocin).



I'm not saying that these compounds overlay, cuz I haven't done the comparison. However, they're pretty close. First, remember that 5-MeO-DMT has a greater affinity in general for the serotonin receptors than does 4-MeO-DMT. So, the methoxy in the ORG compound and the methoxy group meta to the bromine in your proposed compound would overlay the methoxy in 5-MeO-DMT. Then the amine (I'd propose making it a secondary or tertiary amine) in your compound would overlay somewhat closely with the amine in the ORG compound and the tryptamines.

You can figure out the rest of the similarities. It's worth noting that the ORG compound has a higher affinity for the 5-HT2C receptors, and it has a low efficacy at all of the serotonin receptors. It's also worth noting that 2-bromo-LSD isn't a psychedelic although it has affinity for the 5-HT2A receptor.


----------



## dread

dread said:


> When they say that Fencamfamine is a partial DA releaser and a partial DRI, how exactly does that work? Does it reverse some DAT:s and inhibit others? Or does it bind to the DAT and then only reverse it occasionally? Or is there some completely different mechanism?
> 
> Wiki says it releases DA by the same mechanism as amphetamine, but does not say what mechanism it uses to inhibit the reuptake.



So anyone got an answer for this?


----------



## surrеalist

Yeah, that is strange. I was under the impression that a DAT inhibitor bends the transporter so that neurotransmitters can't be pumped out of the synapse, and DA releasers bend and make some "channel" in the transporter that allows dopamine to flow into the synapse from presynaptic vesicles, with the concentration of dopamine trying to reach an equilibrium. This is opposed to normal DAT function which pumps against the concentration gradient.

I bet this is an example of multiple binding sites on DAT- fencamfamine must have affinity to both the phenethylamine DAT-phosphorylating site and to somewhere else, the phenyltropane site perhaps.



Enkidu said:


> I'm not saying that these compounds overlay, cuz I haven't done the comparison. However, they're pretty close. First, remember that 5-MeO-DMT has a greater affinity in general for the serotonin receptors than does 4-MeO-DMT. So, the methoxy in the ORG compound and the methoxy group meta to the bromine in your proposed compound would overlay the methoxy in 5-MeO-DMT. Then the amine (I'd propose making it a secondary or tertiary amine) in your compound would overlay somewhat closely with the amine in the ORG compound and the tryptamines.


Thanks, I'm still preplexed over several things, and it sucks that things aren't as consistent as I thought. I was thinking that the more selective 5-HT2A agonists make for better drugs, but who knows. LSD has nearly equal 5-HT2C affinity as 5-HT2A. I think it's even an antagonist at some.





Here's a poor sketch. Black is 5-methoxy-4-hydroxy-DMT, red is the compound I suggested, and blue is the ORG compound. You might be right that the red compound will behave better as a secondary or tertiary amine, but I'm a bit skeptical because for some reason that kills activity in phenethylamines. Putting the equivalent of an a-methyl group is probably acceptable.


----------



## Enkidu

Well, I haven't seen any papers on the theory behind the development of the ORG compound. However, since the ORG compound is a secondary amine, we should surmise that, if it had to bind in either the tryptamine orientation or the phenethylamine orientation, we should choose the tryptamine orientation.  

The current opinion (as far as I can tell) is that the 5-MeO in 5-MeO-DMT does not overlay the 2-MeO in phenethylamines.

Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.


----------



## seep

Enkidu said:


> Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.



Blue's methoxy has a steric effect on its pyrrolidine, as does the saturated portion of the indane.


----------



## hamhurricane

quick question about agranulocytosis (specifically levamisole induced) 

are existing agranulocytes destroyed, or is it only the formation of new cells which is inhibited? if one uses contaminated cocaine (or aET for that mater) can a single administration produce dangerous results or is it a cumulative effect that requires repeated administration? also how long do the effects last after a single admin. of an agranulocytosis causing drug, eg if one waits a week is that enough time to let the cells regenerate?


----------



## Hammilton

Enkidu said:


> Well, I haven't seen any papers on the theory behind the development of the ORG compound. However, since the ORG compound is a secondary amine, we should surmise that, if it had to bind in either the tryptamine orientation or the phenethylamine orientation, we should choose the tryptamine orientation.
> 
> The current opinion (as far as I can tell) is that the 5-MeO in 5-MeO-DMT does not overlay the 2-MeO in phenethylamines.
> 
> Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.



I don't think it was either.  doesn't seem available now.

Anyway, I've always thought that the ergolines would bind more similarly to phenethylamines.  But unfortunately what people think has generally been found to be wrong.

Anyway, I'm wondering if anyone is aware of analogues of benzodifuran w/ the oxygen replaced by NH?  It could still accept a H-bond (though as I understand a secondary amine forms much weaker H-bonds, correct?).  Thiophene and furan analogues of indoles are active, if less potent.  What about of the dragonflys though?  I have a feeling it's been done, but I don't remember seeing it.


----------



## dread

> I have a feeling it's been done, but I don't remember seeing it.



I also have similar feeling. I seem to remember someone talking about a dragonfly derivative where one of the furans was changed to a pyrrole, but I'm not sure if that was more chemical masturbation or a reference to an actual chemical.


----------



## opiaddict

*meth symthesis*

I recall our oragnic chemistry teacher showing us the synthesis of methamphetamine. Not that I would try, but curious from a biochemical point of view my question is this: why can't you use ephedrine as a starting product and do a reduction on the =0  by usimg a strong reducing agent like Kmno3/LiAl hydride? It made sense when I drew it out, and then I think there may be just a methyl group to add. I don't know. Why is the process such an endothermically contained reaction? I mean, why can't you by pass all these steps and do an addition rx + a reduction?


----------



## opiaddict

I am sorry I meant KMNO4 as a reducer.Or am I off base here?


----------



## N0 W4RN1NG

opiaddict said:


> I am sorry I meant KMNO4 as a reducer.Or am I off base here?



For starters, KMNO4 is a strong oxidizer, you're not going to get methAMP as a result...


----------



## dread

For another thing, there's no ketone on ephedrine, only a beta-hydroxyl. And another thing, no fucking synth discussion.


----------



## Metcalf

*MDA-NBOMe*

I'm not too pharmacologically savvy.  Is this compound potentially active? (in the vein of 2CB-NBOMe)


----------



## nuke

Metcalf said:


> I'm not too pharmacologically savvy.  Is this compound potentially active? (in the vein of 2CB-NBOMe)



I doubt it, as I recall the amphetamine derivatives in that paper lost their affinity for 5HT2 receptors.


----------



## Alotsa

*Turning hearoin into a less potent product?*

There is a lot of information and theories out to make heroin from lesser opiates. 

But what if you wanted to Take Heroin and make it less potent? 

Is this possible to break down heroin into a less extreme drug more like pod tea. methadone, Oxycontin, or even hydrocoden?  possiablr dilute it enough for oral ROA? something? 

Why would i ask such a question? well I don't want something as strong as heroin and It's very hard to find pills for me and when i do they are quite expensive. I think a lot of people who are heroin addicts could had avoided that if it wasn't so much cheaper than pills ( though i cant say from experience). 

Any one elase though of this?  Is there any information on a process to do this? And Has any one successfully done this? 

I live on the west coast and imagine the only herion i could optain would be that of the black tar verity.


----------



## nuke

You can eat heroin, it's just not very bioavailable (~30-40% IIRC).  If you expose it to either an acid or base it breaks down into acetic acid and morphine.

Once you stop doing lots of morphine/heroin you're going to find yourself not wanting to make it any less strong really quickly.

Anyway, no synthesis discussion.


----------



## any major dude

nuke said:


> I doubt it, as I recall the amphetamine derivatives in that paper lost their affinity for 5HT2 receptors.



Is MDA's activity mediated by 5ht2 receptor subtypes?  I recall it having affinity for 2b, but not much for 2a or 2c, IIRC.


----------



## /navarone/

Treating your heroin with sodium hydroxide (or mybe even concentrated baking soda) will yield up in morpine and sodium acetate.






Then you can turn it into another esterified opioid with a lil chem knowlegle


----------



## /navarone/

Hammilton said:


> It's metabolised by MAO very rapidly, for one.  For two, I don't believe it has enough (any?) 5HT2a affinity.  I'm having trouble



I guess you forgot to mention that even DMT is completely metabolized by MAO (in the digestive track i think)
Hence why DMT is smoked in pipes or sometimes idiotically insufflated since i heard reports that its burns like f**k and tastes like s**t when it drops down the mouth.
MMT (monometyl T) is also a mild psychedelic but far from DMT and it will also get annihilated by MAOa.

However it seems that bufotenin and 5-MeO-DMt doesn't get attackes as much by MAO.
In fact 5-Meo-DMT is active orally at 30mg and up to 2 milligrams when inhaled/injected (unlike DMT which is active at a dose of 15-30mg when inhaled).

That's the reason why the DMT containing _Ayahuasca_ infusion drinks, (a very popular 'tea' in some parts of South America), is orally active.
Magic? No, its due to the presence of MAO harmala alkaloids in their infusion.

Also I think that the heavily methylated amine changes the polarity of the amine (increasing structure and lipophilicity) and thus increasing the psychedelic effect and 2-HT2a receptor affinity.
I, wihout reference unfortunately, can somehow relate that to the differences d-amphetamine, d-methamphetamine and d-dimethylamphetamine.
_______________________

BTW i found this on wiki:

*The bio syntheis of endogenous DMT*






Dimethyltryptamine is an indole-alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarized in the picture to the left. In plants, the tryptophan is produced endogenously where in animals the tryptophan used comes from diet. No matter the source of tryptophan, the biosynthesis begins with the decarboxylation of L-tryptophan (1). Once decarboxylated, tryptamine (2) is dimethylated by S-adenosyl-methionine (SAM) via nucleophilic attack. This reaction is mediated by tryptamine-N-methyltransferase enzyme. This produces the product (3). The mechanism has been proven by radio labelling of SAM with carbon-14. The study found that various mammal tissues contained enzymes capable of performing the above transformation.

EDIT:
It would be fun coming up with a drug that enhanced SAM, That would make you dream like fuck since ,FWIH, DMT plays a big role in dreaming.


----------



## MurphyClox

/navarone/ said:


> EDIT:
> It would be fun coming up with a drug that enhanced SAM, That would make you dream like fuck since ,FWIH, DMT plays a big role in dreaming.



Considering the large number of biological reactions that are performed with the aid of SAM, this suggestion is just pointless.


----------



## hamhurricane

*Disposal of JWH-xxx in the UK*

correct me if im wrong, but the scheduling of the JWH and CP series chems in the UK seemed to happen around xmas with no prior government warning. im sure we all noticed how overnight the cannabinoids in question disappeared from vendor menu's but my question is this - if the scheduling did appear without warning how can vendors be expected to dispose of their stock before its too late? if there was warning is their some official protocol for disposal of chems which are on the verge of scheduling - simple toilet flush?

if thats the case i wouldn't be surprised if the english waste treatment facilities were encountering floes of JWH-018.


----------



## kayenta

I remember it being announced about a month beforehand that they were going to be scheduled.

How vendors get rid of their stocks I have no idea...


----------



## nuke

This has nothing to do with pharmacokinetics.  This is toxicology or pharmacodynamics.

It's thought that 4-FA is not a neurotoxin, at least from studies done on rats.  UTFSE for older threads on the topic.


----------



## seep

How many moles of ethanol are in a liter of 40% ethanol-by-volume beverage?

This is not as simple a question as it may seem. A liter of 40% ABV vodka *does not* contain 400 mL ethanol, so volume times density divided by molar mass will give the wrong answer (6.85 moles).

If I simply could find a reliable source that gives the specific gravity of an arbitrarily small quantity of unflavored 40% ABV vodka, then the calculation becomes simple.


----------



## Enkidu

seep said:


> A liter of 40% ABV vodka *does not* contain 400 mL ethanol



Haha, it doesn't? what does it mean then...


----------



## seep

Enkidu said:


> Haha, it doesn't? what does it mean then...



It means that ethanol occupies 40% of the volume. 

But since ethanol and water are miscible, what you have is a fluid matrix of discrete ethanol and water molecules forming and breaking dipole bonds at a temperature-dependent and concentration-dependant rate.

In short, if you stir 4 mL of ethanol into 6 mL of water, at STP, you will form a solution that will be less than 10 mL in volume (even though no mass was lost), and thus more than 40% ethanol by volume.

And by analogy, a liter of 40% AVB vodka has less than the mass equivalent of 400 mL ethanol in it.


----------



## hamhurricane

i was wondering what sweetener is used in adderall IR tablets and when looking at the pill ingredients/excipients i could not find anything that would contribute to the sweetness aside from the saccharate and aspartate salts of dextroamphetamine...possibly? or is the sweetener just not listed, anyone know the answer to this?


----------



## ebola?

that saccharide salt should do the job: saccharine is several times sweeter than sugar by weight.


----------



## seep

ebola? said:


> that saccharide salt should do the job: saccharine is several times sweeter than sugar by weight.











Orange is sweet. Blue is pill-flavored. I dissolve them under my tongue repeatedly. There's gotta be extra sweetener added to orange.

Look at it this way: the orange (a 15 mg Barr) has about 4.6 mg 2.3 mg saccharate and 1.7 mg aspartate. A packet of Sweet 'N Low has 1 gram saccharine. What is the sweetness of 1/200th of a pack of Sweet 'N Low?

*Edit:* The sweetener is lactitol.


----------



## ebola?

i stand corrected.


----------



## any major dude

seep said:


> Orange is sweet. Blue is pill-flavored. I dissolve them under my tongue repeatedly. There's gotta be extra sweetener added to orange.
> 
> Look at it this way: the orange (a 15 mg Barr) has about 4.6 mg 2.3 mg saccharate and 1.7 mg aspartate. A packet of Sweet 'N Low has 1 gram saccharine. What is the sweetness of 1/200th of a pack of Sweet 'N Low?
> 
> *Edit:* The sweetener is lactitol.



i had suspected a sweetener in the orange adderal for some time now.  I guess a smidgin of lactitol makes the medicine go down these days.  How else are we to keep children on speed?


----------



## hamhurricane

does anyone know of a single example of a clandestine drug lab run by a female?


----------



## nuke

Quite a lot of female meth cooks: http://www.informaworld.com/smpp/content~content=a904029899&db=all

Not to mention the very famous LSD chemist Melissa Cargill...


----------



## bleh123

First off, for various reasons, I don't want to cause any permanent neurotoxicity to my brain. Most people say this, but I'm really quite serious about not messing with neurotoxic substances (however tempting it may be to do so). I'm even hesitant to take prescription-strength dosages, because (in my opinion) a slight negative change over a long period of time is a big deal.

I am going to etdPOP(a large electronic music event/rave which is 10+ hours long) at the end of May, and I have heard good things about adderall in settings like this (energy, euphoria, etc)

Would IR or XR be preferable for a setting such as this?  I would consciously keep my body temperature down, and coudl take vitamin c/others if needed. Most importantly, is there a chance of suffering even slight neurotoxicity at this dosage level of 30mg, provided that I keep my temperature down and follow any other prevention measures you guys suggest?

As a separate question: do you think it's worth doing it?


----------



## Germo

I need some info on the side effects of methylon, butylone and of methylone & butylone together. Are they known to produce intense rushes of pain, numb & sore arms and legs like cut off circulation, painful psychosis and a slow onset of stupor . If 1 where to fall asleep in this state would that be as safe as staying awake?
Thank you.


----------



## Germo

I meant to say I need info on these compounds.
Is M1 accumulative.
the M1 and B1 I am talking about both looked smelled and tasted pretty much the same...
Mephedrone and methedrone are good Butylone and Methylone are like poison.
I can not beleive this feeling, if I don't log on tomorrow, I'm prolly dead.
Thank you.


----------



## Germo

Does anyone else smell Xylene and HCl acid all through there head on M1?


----------



## lazydullard

I think you're having postual hypotension and absurd panic attacks and stimulant psychosis and malnutrition. Errr. so fo' sure you're killing yourself. Please go to the hospital? If you still can.


----------



## Dresden

Hi.  I have a quick and not so advanced chemistry ? that has nothing to do with drug synthesis per se for once.  

benzene --> phenol

is a facile enough transformation i guess as it involves the thermodynamically favorable process, ie exothermic oxidative combustion of a simple HC by O (ie, 'burning'), but what about its reverse rxn?

benzene <-- phenol

I have always been under the impression that this pathway is all but impossible but <vecktor> has recently mentioned something involving OTT leaving groups and thallium that has my curiousity piqued.  Is this reverse rxn feasible chemically and if so how specifically?  thx.


----------



## Dresden

_originally posted by hamhurricane:_

Does anyone know of a clandestine chemistry lab run by a female?

Yes, plenty.  Happens all the time.  It's a lot easier to pull of crafty high risk high drama sleights of hand like that when you seem so young and innocent and are also not The Man in charge of the department.

_What are little girls made of?  Sugar and spice and everything nice!_


----------



## mukaki

The wikipage on Kanna says that it should not be combined with SSRIs MAOIs, cardiac medication and psychiatric medication in general. I can't find the reference for that statement and I don't understand why it shouldn't be combined with psychiatric medication and cardiac medication and more specific, what kind of medication in these two groups it shouldn't be mixed with. Hope this is the right place. 

The SSRIs and MAOIs I can understand, but the others? Can anyone enlighten me?


----------



## hamhurricane

^^^
its probably fine, titrate from a low dose and be aware of potential adverse reaction i assume they are just being super-cautious as there might be a chance of hypotension or something. 


QUESTION: i have a vague memory of a paper (perhaps referenced by shulgin?) regarding an experiment that demonstrated claviceps fungus or something of that nature could biosynthesize LSD under certain (experimentally manipulated) conditions - does anyone know what im talking about?


----------



## vecktor

hamhurricane said:


> QUESTION: i have a vague memory of a paper (perhaps referenced by shulgin?) regarding an experiment that demonstrated claviceps fungus or something of that nature could biosynthesize LSD under certain (experimentally manipulated) conditions - does anyone know what im talking about?



yes I know the paper you are thinking of, I think it is published somewhere unexpected like Nature, the researcher was English and I think the reference to it is in the Merck index, not got it to hand. They basically screwed around with the broth in submerged claviceps culture to get a mixture that included LSD I am pretty sure they were using C paspali.


----------



## vecktor

Dresden said:


> Hi.  I have a quick and not so advanced chemistry ? that has nothing to do with drug synthesis per se for once.
> 
> benzene --> phenol
> 
> is a facile enough transformation i guess as it involves the thermodynamically favorable process, ie exothermic oxidative combustion of a simple HC by O (ie, 'burning'), but what about its reverse rxn?
> 
> benzene <-- phenol
> 
> I have always been under the impression that this pathway is all but impossible but <vecktor> has recently mentioned something involving OTT leaving groups and thallium that has my curiousity piqued.  Is this reverse rxn feasible chemically and if so how specifically?  thx.



an example of phenol to benzene conversion, there are loads of variations and this chemistry is very useful in natural products chemistry.

http://linkinghub.elsevier.com/retrieve/pii/S0040403900852624

First the phenol is converted to its triflate ester prior  to the reaction the triflate group is a good leaving group more importantly it cleaves off taking the phenol oxygen with it and is replaced by palladium, the palladium complex is then reduced to liberate the benzene in this case and is then free to react with another aryl triflate.

Ironically phenol from benzene is actually difficult!!!

thallium is used to selectively metallate the 4 position of indole as in the following example

http://www.erowid.org/archive/rhodium/chemistry/lysergic.hendrickson.html


----------



## Dresden

Thanks, vecktor, palladium is just such a damned useful element.

Phenol can be had from benzene by formylation followed by treatment with hydrogen peroxide.


----------



## hamhurricane

thanks vecktor, i found something quite similar in nature detailing the production of lysergic acid methylcarbinolamide and Lysergic acid hydroxyethylamide, but nothing referencing LSD just close relatives. if anyone is able to find this paper i would be very thankful for the ref.


----------



## vecktor

hamhurricane said:


> thanks vecktor, i found something quite similar in nature detailing the production of lysergic acid methylcarbinolamide and Lysergic acid hydroxyethylamide, but nothing referencing LSD just close relatives. if anyone is able to find this paper i would be very thankful for the ref.



I remembered right, surprised really given the onset of senility here. entry 5665 in the Merck index  12th edition Lysergide, Microbial formation by Claviceps paspali over the hydroxyethylamide: Arcamone et al Proc. Roy. Soc (london) 155B 26 (1961) 
The royal society has screwed around with its journals and I couldn't find the paper online, I once read a paper copy it was not very efficient if I remember right.


----------



## Dresden

Wow, that's some sick science.

_bubble, bubble, toil, and trouble!_


----------



## MurphyClox

vecktor said:


> I remembered right, surprised really given the onset of senility here. entry 5665 in the Merck index  12th edition Lysergide, Microbial formation by Claviceps paspali over the hydroxyethylamide: Arcamone et al Proc. Roy. Soc (london) 155B 26 (1961)
> The royal society has screwed around with its journals and I couldn't find the paper online, I once read a paper copy it was not very efficient if I remember right.


DOI: 10.1098/rspb.1961.0056

No access to me; therefore just the DOI and not the full paper.

- _Murphy_


----------



## Cloud_9

Sorry if this has already been asked but what is the safety profile of the SSRE "Tianeptine" or brand-name of "Coaxil?" The Wikipedia entry has an entry about someone taking many _hundreds_ of tablets a day for a 6-month period and it resulted in nothing more than a need to quickly stop administration of the drug as I can't even imagine what he/she was aiming for. 

I am going to be in the Russian Federation this summer and am trying to find a semi-comprehensive list of what exactly is more legal in the C.I.S. states than perhaps in the USA or Europe even. I am looking forward to both large amounts of Carphedon/Phenyl-Piracetam which is a nootropic-style stimulant, and the aforementioned Tianeptine/Coaxil. Any comments on these two choices or very-obvious other drugs I should be dipping my nose towards?

Edit: Want to know a bitch about travelling to Russia? I can't bring my methadone into the country without a special note of exception which I refuse to bribe an official to get; so here's to a taper of awesome speed~!


----------



## ebola?

Obvious, but dude, if you 'need' mephedrone, you should take a break from mephedrone.


----------



## Cloud_9

ebola? said:


> Obvious, but dude, if you 'need' mephedrone, you should take a break from mephedrone.



Methadone is not equal to mephedrone. I've done it before too, don't worry; they are very much too-similar. I vote a name change and/or we will start using 4-MCC as its proper chemical classification!


----------



## Captain.Heroin

Cloud_9 said:


> Methadone is not equal to mephedrone. I've done it before too, don't worry; they are very much too-similar. I vote a name change and/or we will start using 4-MCC as its proper chemical classification!



I already call that crap 4-mmc as is!


----------



## RGB

I feel kind of foolish for asking this being an ED moderator and all, but I have a few questions about MDMA that have been bothering me for a while. Some of them are more assumptions than questions, so I'll just state those and you can disagree with them if they're wrong.

I'm also going to ignore MDMA's effect on DA and NE for the time being, because I assume that those systems are less likely to be significantly disturbed by occasional MDMA use.

First off, what exactly does it mean for SERT to be "reversed" by MDMA? Does 5-HT just start spilling out of the transporter or is some other action required (for instance, 5-HT binding with the transporter on the outside for reuptake)? Does this "5-HT dump" only in the brain or in the PNS as well, and if it does occur outside the brain does it have any known side-effects? I imagine that it would cause some gastronomic and vascular issues, since 5-HT also mediates those systems.

Also, is the amount of 5-HT released proportional to the dose, or is there a critical dose over which a "serotonin-releasing cascade" begins, releasing some percentage of one's total 5-HT reserves regardless of additional dosage? Is it even correct to think of MDMA as releasing a percent of one's 5-HT, or is it better to think of it as tipping the scale toward greater release over production? Since 5-HT is constantly being produced, it seems unlikely that one could "run out of serotonin". Is it even possible to function with no serotonin left? Does the brain somehow increase serotonin production after depletion?

I think I'll stop there, but I have a few more questions which I'll pose depending on the response to these ones. I greatly appreciate any answers at all.  Thanks!


----------



## dread

Well I'm not an expert but AFAIK it goes like this: SERT moves serotonin from the synaptic cleft into synaptic vesicles, and MDMA binds on the SERT protein and changes it's conformation so that this action reverses, and SERT will start moving serotonin from the vesicles to the synaptic cleft. As a side-effect some MDMA molecules will find their way in the vesicles, which causes neurotoxicity... 

I might be completely wrong here, that's just the impression I got.


----------



## RGB

That makes sense, thanks. 

I suppose I'm just not clear on the "reversal" bit -- what does that mean in a functional sense? As far as I understand, once the reuptake transporter into a vesicle it floats around freely inside the cell until an action potential causes the vesicle to merge with the cell wall, releasing its contents outside the cell. Does the transporter in its reversed state actually attract serotonin-filled vesicles and release their contents outside the cell? This seems strange to me, but would be a "reversal" of its usual action.

On the topic of neurotoxicity, is it known that it's a direct metabolite of MDMA that causes neurotoxicity? Has the dopamine theory been discounted by now? We're a little behind the times on interpreting the research on ED, unfortunately.

Perhaps this warrants its own thread on second thought...I'm not too clear on the ADD protocol.


----------



## Dresden

Yes, it is known that a direct metabolite of mdma causes the purported neurotoxicity.  Mdma itself directly added to the brain does not cause neurotoxicity at recreational doses.  The metabolite is 3,4-dihydroxy-methamphetamine.


----------



## ebola?

AFAIK (not a pro in this area), there's some sort of synergy of mechanisms that effect MDxA's neurotoxicity.  Basically, conditions that combine to promote the formation of free-radicals and those free-radicals' entry into neural cell bodies are to blame.  So these include increased body-temperature (hence the lack of neurotoxicity of MDMA administered to the brain directly (5ht and the catecholamines increase body temperature...as does dancing to up-tempo music :/)), toxic metabolites of MDxA itself, and then entry of toxic metabolites of dopamine into cell bodies via SERT (these metabolites formed either within or without the cell).  The latter explains why selective 5ht releasers don't exhibit neurotoxicity.

But I'm less of an expert than the above people claiming a lack of expertise. 

ebola


----------



## ebola?

What do we know about the neurological effects of 2-aminoindane (unsubstituted)?  To the extent that we remain ignorant, what do y'all speculate?


----------



## Damien

heh, thought you guys might enjoy this:


			
				Westheimer's Discovery said:
			
		

> A coupla months in the laboratory can save a coupla hours in the library.


----------



## hamhurricane

i might start a thread for this if nobody objects but im wondering how many ADDers are going to be at the upcoming MAPS conference - i will be.


----------



## naginnudej

Can anyone discuss the reality of this statement regarding 4-fluoroamphetamine?



RedLeader said:


> Chemically, well ya on some rather-rudimentary levels it's pretty close. But 4-fluoromethcathin's structurally going to be closer to 4-fluoromethcathinone (4-FMC), which carries all of the physical dangers of 4-methylmethcathinone (4-MMC). So by transitivity, the stuff's going to be pretty darn close to mephedrone, for better or WORSE.
> 
> Meaning the risk of neurotoxicity (mainly), as well as addiction, is also going to be higher than the more classical amphetamine phenethylamines (like MDMA), given (among other things) that it's more closely related to mephedrone than to MDMA.


----------



## ebola?

I think that I lack some of the context that could situate RedLeader's original post, but 4-fluoro-amphetamine has been found to carry drastically less risk of neurotoxicity than mdma, as is largely the case with methylone too (both studies are Nichols et al., iirc).  Also, I don't see why we should consider mephedrone more neurotoxic than MDMA on an a priori basis.  As of yet, we don't really know what its receptor affinities, etc. are like, even.

ebola


----------



## naginnudej

ebola? said:


> I think that I lack some of the context that could situate RedLeader's original post, but 4-fluoro-amphetamine has been found to carry drastically less risk of neurotoxicity than mdma, as is largely the case with methylone too (both studies are Nichols et al., iirc).  Also, I don't see why we should consider mephedrone more neurotoxic than MDMA on an a priori basis.  As of yet, we don't really know what its receptor affinities, etc. are like, even.
> 
> ebola



That was the answer I was looking for, thanks.

Have any thoughts about cardiodoxicity of 4-fa? Should one be worried about similar side effects that meph presents?


----------



## ebola?

I don't think that there's been rigorous study on the danger of 4-fa's metabolites (although they've been identified), but I believe that you have little to worry about--4fa won't metabolize to an ephedrine-like compound (in this case, we'd be worried about a cathine derivative, I believe).

5ht2b agonism is a more open question.  If you have enough 4fa for this to become a legitimate worry, I envy you...A LOT.


----------



## jaguraguguru

Yeah usually heart issues, such as those caused by 5ht2b agonism, don't appear until years of heavy abuse of serotonergic stimulants. But I'd say it's almost 100% certain that 4-FA would cause this effect over time with heavy abuse.


----------



## Metcalf

*1-(4-methylphenyl)-2-aminobutane*

Does anyone have any information about this compound?


----------



## ebola?

Please try not to cross-post (I see that you made a distinct thread for this compound).
I can also see why you're perplexed--a google search pulled up pretty much your own threads alone.

ebola


----------



## Metcalf

Sorry, I put it here first, and then got worried it might not get any attention.  I wasn't sure how active this thread was.  You can delete whichever you think is less relevant.


----------



## phase_dancer

It's available from some legit chem suppliers as 1-(4-methylphenyl)butan-2-amine


----------



## allium

Hello!

I am a layman. but I am interested in neurobiology. So, first of all, where can I learn the basics of it? Good books and articles to start with? I prefer scientific ones.

And I have few questions to ask:
1) Do endorphines play little role in mood control? 
2) Does high serotonin level in bloodstream not necessarily mean high level in brain? What about other monoamines?
3) Are there any theories explaining love from the neuroscience point of view? Recently I read a theory about different stages of love(PEA stage, Adrenaline stage, Amphetamine stage, Dopamine stage...). It looked like a bad pop-science article, but is there any similar scientific theory, so I can read the original.
4) And the last one: can amphetamine be produced in the body of a norman human? I mean, is there endogenous amphetamine(not a similar compound like phenylalanine, but amphetamine)?


----------



## white_widow

allium
your best bet is to look through medical journals...good old fashioned libraries are great for this sort of thing. The reason they're so useful is because at the end of every article there are citations and indications for further reading. That way, you can find articles that interest you, read them, decide if it's worth pursuing, and go from there. 

I've been a self-teacher in this respect for a long time, but I should qualify that I'm a pre-med student with easy access to an excellent library and a startling obsession with medicine.

Either way, hope you find it helpful.


----------



## The Smoking Man

I was thinking about this earlier today. Tryptamines substituted on the 5 position like to have nasty sympathomimetic effects. What if you had a chemical, for example, 5-methoxy-dimethyltryptophan, perhaps coadministered with a peripherally active-only dopa decarboxylase inhibitor (definitely if taken orally)? Could such a prodrug act as a good way of increasing its concentration in the CNS and decreasing peripheral concentration? The molecule would still be able to exit out the blood-brain barrier, so it wouldn't _eliminate_ peripheral activity, but it could still cut back on it significantly. Or would tryptophan hydroxylase still try to mess with the 5 position even though there's already something there? If that's the case, then could at least, say, dimethyltryptophan (5-hydroxy-dimethyltryptophan would be better actually) act as a good prodrug for bufotenin? The only other problem I can think of is, in the examples I've given, is that they have a relatively short duration of action. If dopa decarboxylase is too slow and MAO is too fast, then this would be inefficient and/or ineffective.

Edit: Wait, can you even have a dimethylated tryptophan that would be decarboxylated by dopa decarboxylase to produce the desired molecule anyway? I'm having my doubts about this.

Edit 2: Seems Shulgin disagrees with this idea.


----------



## ebola?

Maybe this would be better suited to psychedelic drug discussion, but. . .

Which psychedelics, particularly those still available on the US's grey market, present the fewest cardiovascular risks?  My 'gut' would say one of the psilocybin-like tryptamines, but this is going off subjective feel.  What about the 2Cs?  Is the tension (and headaches) that they effect due to adrenergic agonism, best avoided if one is steering clear of cardio-strain?  Or are these types of discomforts essentially benign?

This time, I'm truly asking on behalf of a friend (7 hours of cardio a week BETTER render me healthy enough for stimulating forays ).  I know that psychedelics and heart conditions don't mix, but I also know that people can be too damned stubborn. 

ebola


----------



## nuke

The partial agonism of the tryptamines and 2c-x drugs lead me to believe that they're more benign...  The biggest thing to look for is any instance of fatalities which has only ever really happened with 2c-t-7 in the 2c-x family and 5-MeO-DMT (when combined with MAO-Is) in the tryptamine family.  I really don't think there's much to worry about with most of the phenethylamines, there seems to be a greater body discomfort to some people but it's never translated into anything life-threatening even in heroic doses.

Except for probably cannabis, I'd imagine that these psychedelics are probably some of the safest recreational drugs out there except in terms of psychosis risk (which cannabis has, too).

The psychedelic amphetamines, on the other hand, being full agonists, are probably more dangerous.  The DOB-Dragonfly mix-up a little while back shows just how much.


----------



## nuke

allium said:


> Hello!
> 
> I am a layman. but I am interested in neurobiology. So, first of all, where can I learn the basics of it? Good books and articles to start with? I prefer scientific ones.
> 
> And I have few questions to ask:
> 1) Do endorphines play little role in mood control?
> 2) Does high serotonin level in bloodstream not necessarily mean high level in brain? What about other monoamines?
> 3) Are there any theories explaining love from the neuroscience point of view? Recently I read a theory about different stages of love(PEA stage, Adrenaline stage, Amphetamine stage, Dopamine stage...). It looked like a bad pop-science article, but is there any similar scientific theory, so I can read the original.
> 4) And the last one: can amphetamine be produced in the body of a norman human? I mean, is there endogenous amphetamine(not a similar compound like phenylalanine, but amphetamine)?



1.) No clue, I imagine opioid agonists would cause profound mood changes though
2.) I could imagine situations where it would not, but generally it does
3.) I doubt that there's much more than theories out there, and studies quantifying various chemicals at various stages
4.) No, amphetamine is synthetic and not encountered in any organisms as far as I know, hence its ubiquitous activity as a stimulant in most mammals


----------



## The Smoking Man

nuke said:


> 4.) No, amphetamine is synthetic and not encountered in any organisms as far as I know, hence its ubiquitous activity as a stimulant in most mammals


http://www.cognitiveliberty.org/shulgin/adsarchive/acacia.htm


----------



## nuke

The Smoking Man said:


> http://www.cognitiveliberty.org/shulgin/adsarchive/acacia.htm



It is well known that this has been debunked as contamination


----------



## KAYLA2010

allium said:


> Hello!
> 
> I am a layman. but I am interested in neurobiology. So, first of all, where can I learn the basics of it? Good books and articles to start with? I prefer scientific ones.
> 
> And I have few questions to ask:
> 1) Do endorphines play little role in mood control?
> 2) Does high serotonin level in bloodstream not necessarily mean high level in brain? What about other monoamines?
> 3) Are there any theories explaining love from the neuroscience point of view? Recently I read a theory about different stages of love(PEA stage, Adrenaline stage, Amphetamine stage, Dopamine stage...). It looked like a bad pop-science article, but is there any similar scientific theory, so I can read the original.
> 4) And the last one: can amphetamine be produced in the body of a norman human? I mean, is there endogenous amphetamine(not a similar compound like phenylalanine, but amphetamine)?



1. yes
2.There are blood and urine tests that estimate from calculations of the hormone being excreted/flowing in the blood stream.....There are so many different theories about how neurotransmitters work.....but as of today they are tested by measuring the secreted/flow in the blood stream to calculate how much is being made by your glands........
3....I read one time about a gland or something in the middle of your brain/central region of your brain....that produces a hormone that causes feelings/sensations of love...love is actually a side effects of high levels of hormones.......and that probably ruined someones love theory....sorry
4.humans can not make amphetamines on their own....there is a whole process.....and  i might be wrong on some of this....--don't blame me blame my ADD-lol its late and i should probably sleep.......but i will probably just research what i just wrote if i remember after submitting this...


----------



## KAYLA2010

2. means maybe....as of today yes a blood test can produce results....but its really just an estimation because we don't fully understand the brain.....

I really hope that makes sense....


----------



## ebola?

> It is well known that this has been debunked as contamination



A tad more parsimonious than Acacia containing every fucking drug, aye.


----------



## aparenz

*Sulfuric Acid Question*

Why exactly is sulfuric acid most often used for acid catalysis?


----------



## tryp2fun

aparenz said:


> Why exactly is sulfuric acid most often used for acid catalysis?



It is the strongest of the common laboratory acids, so it can form highly reactive intermediates like carbocations the best.


----------



## aparenz

But the pKa of HCl is -7 and the pKa of H2SO4 is -3, so are you saying that sulfuric acid is cheaper?


----------



## nuke

aparenz said:


> Why exactly is sulfuric acid most often used for acid catalysis?



Because it will protonate an alcohol group but it won't react with tertiary alcohols to form alkyl halides through an SN1 reaction.


----------



## aparenz

thanks, answered my question


----------



## aparenz

Whats the name of this molecule: Hg(O2CCF3)2


----------



## dread

Anyone have any information about 4-phenyl-2-pyrrolidone? By what I can tell it should be a prodrug to phenibut, possibly more potent? 

I found a cas number and MSDS for it, but not much else... 

http://www.chemcas.com/msds/cas/msds120/1198-97-6.asp

this says it produces analgesia and "changes in motor function" in mammals... I wonder if it would be worhtwhile in any way? Have any human bioassays been made ever?


----------



## MurphyClox

aparenz said:


> Whats the name of this molecule: Hg(O2CCF3)2



Mercury(II) trifluoroacetate.

- _Murphy_


----------



## aparenz

I've been having some trouble understanding what causes conditions in a reaction to be acidic or basic.

For instance in the formation of a nitronium ion, nitric acid and sulfuric acid are reacted to form a nitronium ion by loss of water. So this happens because the nitric acid is protonated forming water which is an effective leaving group. What exactly gives the nitric acid the urge to become more acidic? Is it because sulfuric acid is more acidic and willing to protonate it? 

Any help with an explanation on acidic and basic conditions in organic chemistry would be greatly appreciated because I've been having trouble incorporating it into mechanisms as needed.


----------



## seep

aparenz said:


> Is it because sulfuric acid is more acidic and willing to protonate it?



"Willing" invites metaphoric confusion. Better to consider the resonance forms of bisulfate ion:






This anion is more stable than the nitrate anion.


----------



## Cloudy

Any recommendations for advanced organic chemistry books?  I've taken two semester of organic and my university doesn't offer higher level classes.


----------



## seep

^March's Advanced or Carey and Sundberg's Advanced.  Either is roughly 2400 pages.

See this offsite thread for discussion


----------



## Cloudy

I know my library has an up to date (2007) March's, and Carey and Sundberg's Advanced from (1990)
thanks for the advice and the link


----------



## Christo_Rey

I'm looking to know more into the mechanism of actions of different drugs, I've seen the Color Atlas of Pharmacology recommended earlier in the thread, is this a good starting point? Any other books to recommend to an amateur?

Reason to ask is : I've been dabbling in RCs for the past few years, and would like to know more about how they work so as to evaluate the dangers of those I'm interested in and better understand the journal articles to make more informed decisions as to what I choose to experiment with (eg to be more aware of the  dangers of the drugs in themselves and also possible interactions with other medications I take... read to many horror stories about this).


----------



## nuke

> Any recommendations for advanced organic chemistry books? I've taken two semester of organic and my university doesn't offer higher level classes.



Wileys Intermediate Organic Chemistry, 2nd Edition

It's weird that your university doesn't have more than 2 organic courses, most offer some kind of stereochemistry heavy upper level ochem course too


----------



## Cloudy

My university only has a few departments that even have a graduate program, and I believe only 2 departments with a doctorate program.  Its a good university, but small (15000 including grad students) and up an coming.  The chem program isn't very good.  I should have thought about this before I went, but oh well...


----------



## JamtasticX

Just got chemoffice08, having fun playing around with it, seems like a great suite so far. Hopefully I'll will advance my  mind on chemistry greatly


----------



## naura

forgive me for the stupid question, but:

isn't cynanide toxic? what would the effects of 2c-cn be in terms of cynanide's ability to inhibit oxygen transport by blood cells (the way it poisons you, i believe)? would this be negated by its being bound in the phenethylamine?

enlighten me, someone who knows more.


----------



## MurphyClox

Cyanide, per definition of the nomenclature, is an *ion*, i.e. CN-. That is the toxic species that inhibits the respiratory chain and, by the way, which is as toxic agents in the US' gas chambers nowadays (and in German gas chambers during 1933-45, too). 

The CN in 2C-CN is bound _covalently_ and for this reason should be called "nitrile", not "cyanide" (this naming is often confused).

The difference is that the former one is an independend molecule, able to reach its target (...CYPs of the respiratory chain), while the latter will stick to the ring until it gets metabolized. I have no idea at the moment what the metabolism for 2C-CN in particular is (if it was ever studied), but usual pathways go e.g.
-CN + water to -CONH2 (by nitrile hydratase)
...followed by -CONH2 + water to -COOH + NH3(by amidase)
-CN + water to -COOH & NH3 (by nitrilase)
-CN + water to -CH=N-OH (by aldoxime dehydratases)​None of these liberates cyanide at any stage.
There _may be_ exceptions, but in general are aromatic nitriles not extraordinarily toxic.

Peace! - _Murphy_


----------



## Slapdragonx

Not extraordinarily, but possibly toxic?


----------



## aparenz

What are a few general guidelines that should be followed when choosing a solvent for a specific reaction?


----------



## MurphyClox

With regard to 2C-CN:


Slapdragonx said:


> Not extraordinarily, but possibly toxic?



I couldn't find any verified data so can only speculate. I'd think the toxicity should approximately be in the range of 2C-B, -C & -D.

Cyanide toxicity is not expected in this case. But lets consider the unlikely (and furthermore unrealistic) scenario of quantitative cyanide-release from 2C-CN for a moment:
Shulgin lists 2-40 mg as common dosage, therefore I will calculate with the median, 30 mg. The molar weight of 2C-CN is 242.7 (as hydrochloride salt), a dose of 30 mg equals therefore 123 µmol. Wikipedia lists the letal dose for cyanide (CN-, not KCN or NaCN) as ca. 140 mg, which equals 5.4 mmol.
Relating these values, one can see that even upon quantitative release of cyanide from 2C-CN, the lethal dose is still 43 times larger.

Ergo: Cyanide poisoning, either with a  lethal or sublethal dosage, is far unrealistic both from the metabolic perspective (see my last post above) as well as from the consumed amounts.


Take care!

- _Murphy_


----------



## MurphyClox

aparenz said:


> What are a few general guidelines that should be followed when choosing a solvent for a specific reaction?



1. Synthesis-discussion and even synthesis-related topics are forbidden here!

2. Anyway, to answer in short: Your question is too sketchy to be answered properly.
It really depends on _a lot_ of criteria, for example the reaction's mechanism, solubility of reagents, required reaction temperature, ...

Without further info, there's no answer possible. Well, but adding more details brings us directly back to 1. 


- _Murphy_


----------



## Christo_Rey

Question: bk-MDMA has been patented by Shulgin (1996) as an antidepressant. Is anyone aware of actual clinical trials that were done with it, and where I could read about them?

Don't know if it's the best thread to ask this, but don't know where else to ask.


----------



## alexi

Cloudy said:


> Any recommendations for advanced organic chemistry books?  I've taken two semester of organic and my university doesn't offer higher level classes.



Clayden's "Organic Chemistry", by a long way


----------



## seep

*Suggested reading order for Pihkal?*

What order should I read Pihkal (part 2) in if I want to read it as a narrative?

That is: everything was cooked up and ingested in a certain order, and that order wasn't alphabetical. Is there a chronological index (or something along those lines) somewhere?


----------



## dread

Aren't the entries numbered chronologically? I always thought they were.


----------



## seep

^Doesn't seem that way to me.  Even in compound #1 (alpha-ethyl mescaline) he has this whimsical passage (red text shows references to past events):



> The extension of the two-carbon chain of mescaline by alpha-methylation to the three carbon chain of TMA approximately doubled the potency of the compound. And it was felt to be a completely logical possibility that, by extending it one more carbon atom, to the four carbon chain of alpha-ethyl-mescaline, it might double again. And following that logical progression, the doubling of potency with each additional carbon atom, the factor would be 2 to the 7th power by the alpha-octyl (or 256x that of mescaline, or a milligram as active dose) and with a side chain of a 70-carbon alkyl group (alpha-heptacontylmescaline) it would take just a single molecule to be intoxicating. This was rich fantasy stuff. As an active compound, just where would it go in the brain? With an 80-carbon side-chain, would one-thousandth of a single molecule be enough for a person? Or might a single molecule intoxicate a thousand people? And how long a chain on the alpha-position might be sufficient that, by merely writing down the structure on a piece of paper, you would get high? Maybe just conceiving the structure in your mind would do it. That is, after all, the way of homeopathy.
> 
> Maybe it was just as well that this added two-carbon side-chain with lowered activity was already enough to disprove the doubling pattern.



The implication is that 3,4,5-trimethoxyamphetamine (TMA, #157) had already been synthesized and assayed, was found to be twice as potent as mescaline, and Shulgin then set out to test whether longer alpha-alkyl extensions would show a continual escalation in potency. In this vein he synthesized and assayed AEM.  

Plus, from an administrative standpoint, common families have common precursors (obviously ordered in bulk), and some of these have poor shelf lives.  Why place yourself in a position in which you have to continually discard and reorder precursors when you can utilize economies of scale to streamline your budget?


----------



## nuke

As many of the items in PiHKAL were synthesized in part and then shelved and returned to later, it's difficult to get a chronology for the compounds.  The same thing goes for the bioassays.  The closest thing you'll get to chronological order would be the stuff in the first books of PiHKAL/TiHKAL.

You can also go through Shulgin's list of publications to see when he published about various compounds.


----------



## x89

Perhaps an easy one: Where's a good place for one with mediocre knowledge of chemistry but 168 hours a week of free time and a burning desire for knowledge to self teach this stuff. Are there any areas which are easier to start on? I believe the encompassing subject is called "Organic Chemistry" am I right?!
Computing is my area of expertise but that's a dawdle!


----------



## aparenz

Anyone looking to hone their OChem skills I found this page to be rather useful.

http://evans.harvard.edu/problems/index.cgi


----------



## DavisK4high247

I cannot find any info on any websites on this medicine I got for nasal use after a surgery 2 days ago( cocaine and neosynephrine nasal drops ) can anyone help me find the chemical makeup of these drops and in what amount of each drug is prsent in this soulution and maybe the ph of the solution,it says saline cocaine drops with noesynephrine and it stops the bleeding and somwhat dums the stiched up area but does not seem to absorb into the bloodstop nasaly or through the stitced area which are still fresh and should absorb any cocaine into the bloodstram unless it is ph designed or something to be non soluble internasaly to absorb more that at a very small localized are? any help would be appreciated and as quicky as possible as well would be of great help.Thank You


----------



## nuke

x89 said:


> Perhaps an easy one: Where's a good place for one with mediocre knowledge of chemistry but 168 hours a week of free time and a burning desire for knowledge to self teach this stuff. Are there any areas which are easier to start on? I believe the encompassing subject is called "Organic Chemistry" am I right?!
> Computing is my area of expertise but that's a dawdle!



Buy yourself a copy of vogel's practical organic chemistry...  I started with organic chem instead of generalized chem and it treated me fine.


----------



## Xynthetic

What does the "N" refer to in IUPAC nomenclature?


----------



## phase_dancer

It describes substitution on a Nitrogen....e.g. _N_-methyl-1-phenyl-propan-2-amine (methamphetamine); _N,N_-dimethyl-1-phenylpropan-2-amine (dimethylamphetamine)


----------



## brown sugar

hello im new here


----------



## Astavats

*Pharmacokinetics*

I'd like to learn more about metabolization of various drugs, how certain groups may or may not get removed/replaced, and so forth. Does anyone have suggestions where I could begin? Websites, books, texts, videos, anything would be appreciated, especially if it's publicly available.

It's fine if it's ahead of me, I have no exceptions of digesting all the information at once.

All the best.


----------



## phase_dancer

A basic pharmacology text is a good place to start

I found Rang et al "Pharmacology" a fairly good text. 

It's also worth getting an metabolic pathways wall chart. Sigma Aldrich used to have a good free chart.


Here's a few that have been available online as e-books 

Drug Metabolism Current Concepts Edited by Corina Ionescu and Mino R. Caira

Pharmacokinetics and Metabolism in Drug Design
Edited by D. A. Smith, H. van de Waterbeemd, D. K. Walker, R. Mannhold, H. Kubinyi, H.Timmerman

If you're feeling like getting in up to your ears 

Comprehensive Enzyme Kinetics by Vladimir Leskovac


----------



## Astavats

Sounds excellent, thank you for the wealth of sources P_D!


----------



## zero zero

Can this be produced directly from DMT. How does it happen. Where do the other hydrogen atoms go.


----------



## nuke

There are no synthesis questions allowed, but no.


----------



## Ariel438

Greetings to all! I was just birthed(joined) and not 2 b rude or needy... But. Could someone please      
Walk me thru the acetone wash? I'm on my iPod touch which appears to be faulty making it difficult to surf past threads. I apologize for barreling into your conversation


----------



## melange

ok ADD gurus please do not flame - after all I am a college dropout teaching myself, but I assume adding a 3,4 methylenedioxy chain to nardil(Phenelzine) would essentially equal death?


----------



## nuke

Yeah.  Organic hydrazines are really good irreversible inhibitors because of their instability.



> Walk me thru the acetone wash? I'm on my iPod touch which appears to be faulty making it difficult to surf past threads. I apologize for barreling into your conversation



Ok:
1. Put product in filter.
2. Chill acetone.
3. Dump cold acetone onto product.
4. Dry product.
5. Profit?


----------



## UYI

*MDMA IC50 Values*

Just out of curiosity I'm wondering if anybody could tell me the IC50 values for MDMA in relation to serotonin, dopamine and norepinephrine? I have tried Google but it didnt seem to help.

Apologies if this is in the wrong forum.  Thanks.


----------



## nuke

UYI said:


> Just out of curiosity I'm wondering if anybody could tell me the IC50 values for MDMA in relation to serotonin, dopamine and norepinephrine? I have tried Google but it didnt seem to help.
> 
> Apologies if this is in the wrong forum.  Thanks.



Go here: http://pdsp.med.unc.edu/pdsp.php

And select MDMA as the test ligand.

This will not tell you EC50s for monoamine release though, 

The user rocknroll714 compiled a big list of IC50s/EC50s on his wiki too: http://en.wikipedia.org/wiki/User:El3ctr0nika/affinities

I suggest you read up on the methodology by which these tests are conducted too if you want to make a decent amount of sense out of them, it's important to know what the hot ligand (radioligand) was that the new ligand displaced because different ligands can occupy different places in the receptor.


----------



## Further86

*Differences between 5-HT2a and HT 2c*

I've rencentlly begun an attempt to gain a much deeper understanding of the pharmacology of Tryptamines and Phenethylamines. Out of this study I've come across 2 questions which I'm having trouble finding an answer two. Firstly can anyone explain to me the differences in the function of the 5-HT2a and 2c receptors. while i know both are G protein-coupled receptors i''m not sure of their individual functions. Second, What is the difference between partial and Full agonism/antagonism. Thanks for your responses.


----------



## Astavats

Questions like this might be better suited in The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread for future note. Anyway, someone else may correct me but to my knowledge...

5-HT2C: As far as I know, it plays a role in anxiety naturally. The binding site is similar to 5-HT2A which why there is no 'solely 5-HT2A agonist' currently.

5-HT2A: Responsible for 'psychedelic effects' when activated by a drug. It's also plays a role in regulating intraoccular pressure (non-centrally).

Partial agonist v. full agonist: I believe when a drug activates the receptor with lower efficacy than neurotransmitter. On the other hand a full agonist will activate the site with equal (or greater) efficacy than the neurotransmitter.


----------



## Further86

^Thanks a lot, I had a feeling this was the wrong thread, im still learning what goes where. This was actually my first ever post. Your answer definitely helped, i appreciate it.


----------



## any major dude

from what i understand 5ht2a is anxiolytic & 2c is anxiogenic, among other things of course.  Recent article I happened upon mentions this http://www.newscientist.com/article/mg20727703.300-serotonin-cell-discoveries-mean-rethink-of-depression.html


----------



## P A

> opiates suppress immune system



Yes.

And after lurking/eavesdropping on multiple forums/conversations, there still appears to be an inordinate degree of uncertainty regarding the amphetamines' actual mechanism of action. Is this discrepancy still reflected in the literature? Because it seems like those with advanced pharmacological knowledge briskly brush past the topic like it's old news while the rest of the world wonders: HOW does amphetamine phosphorylate the transporter? An allosteric binding site? Some weird direct mechanism as a modifying substrate? Kinase modulation? And is the old 'weak base' theory of amphetamine-mediated monoamine release still viable, or has some academic consensus been reached of which I've been completely unaware? I got tired of scavenging Google Scholar a long time ago, and nothing I found appeared conclusive in the least.

EDIT: In other words, if amphetamine-elicited monoamine release is truly nothing more sophisticated than typical exchange diffusion, then why haven't the DAT, SERT, NET and others been reclassified as functional antiporters? And further, why would this dramatic aberration of basal neurotransmitter release be so highly dependent upon increased intracellular PKC and MAPK? And how would the transporter become/have to be phosphorylated by a kinase-dependant mechanism in the first place if it already exists as an antiporter capable of sucking up these exogenous releasing agents in exchange for the endogenous amines? Or are these researchers actually suggesting that each of the many, _many_ structurally diverse releasing agents each happen to have three separate, essentially identical actions [one extra- and two intracellular] that mediate their effects? That just sounds way too unlikely and convoluted, but again, maybe I'm missing something big here.

Also, does anyone have the nanomolar affinities for dextrorphan at the SERT and nicotinic receptors? I tried extensively UTFSEing, but with no luck whatsoever. And to what extent is methorphan's pharmacology even relevant to its dissociative properties, given its comparatively low affinity for the PCP site? Is its 'recreational' role simply that of a practically inert prodrug, and if so, what's with all the cautionary tales regarding serotonin syndrome? Typical hysteria, or is there something of a biphasic metabolism here? Or is dextrorphan's affinity at the transporter comparable to that of the parent compound?


----------



## Xynthetic

What are the major differences between noradrenaline and adrenaline when they are currently activating their respective adrenergic receptors?

Edit: Another question, although rather off topic: What is the nomenclature behind using the commonly found pyr- prefix in chemistry? E.G. Pyrazole, Pyridine, Pyrocatechol. Does it simply mean its commonly a product of pyrolysis?


----------



## P A

> What are the major differences between noradrenaline and adrenaline when they are currently activating their respective adrenergic receptors?



As a rule, there are no 'respective' receptors for either sympathogen, as their highly analogous structures predicate similar binding profiles. Though this is explanation is highly simplistic, it's generally helpful to pair epinephrine (adrenaline) with the beta adrenoreceptors and norepinephrine (noradrenaline) with the alpha receptors. The former compound has higher affinity for the much more peripherally active and "drastic" and myocardically "potent" of the two subtypes [the beta adrenergic receptors] given its well-known function as a vasomotor pressor agent to be used by the body only in intermittent scenarios of emergency fight-or-flight. The comparatively more "regular" or "mild" adrenoreceptors [those of the alpha subtype] mediate basal ("normal") peripheral neurotransmission, allowing strictly for baseline maintenance of heart rate and blood pressure. In other words, though both ligands have affinity for both receptor subtypes, their differential effects on the peripheral nervous system are mediated by their proportionally selective affinities for one adrenergic receptor subtype over the other. So epinephrine=beta/alpha and norepinephrine=alpha/beta. 

As for the central nervous system, adrenaline's structure denies it access to the brain via diffusion across the blood-brain barrier, making it effectively irrelevant as a central neurotransmitter. _Nor_adrenaline, on the other hand, is the one of the three most prevalent monoamine transmitters in the mammalian brain, with significant effects on transmission reaching from the spine to the brainstem to the cerebral cortex. And while there are still beta receptors in the CNS, they essentially function as nothing more than special low-affinity receptor sites for noradrenaline and are much less widely expressed than their alpha counterparts. And in case you're wondering, noradrenaline is more prevalent due its presence within the presynaptic neurons that release it, both within selected nerve terminals in the periphery and the locus coeruleus within the brainstem. To my knowledge, adrenaline originates [and is released] solely from the adrenal medulla, a specialized gland mobilized only in extreme circumstances of physiological stress.


----------



## Xynthetic

Thank you for the detailed response!

Edit: Also I noticed you said noradrenaline was one of the three most prevalent monoamine transmitters. Are the other two serotonin and dopamine?


----------



## P A

> Are the other two serotonin and dopamine?



Yes indeed.


----------



## mahatoka

If you have a single isomer of a chemical, will it form larger crystals than the racemic counterpart?


----------



## peacelovedope

*How much amphetamine was in Benzedrine inhalers?*

I have been reading On the Road: The Original Scroll and of course, one of the Beats most used drugs: Benzedrine is frequently mentioned.  From what I have read so far, it appears that 1 strip was the optimal dose.

I am curious as to just how much racemic amphetamine was in one of those things.  I have been able to find that the tablets contained 5 mg, but I have had no such luck in figuring out the total amount in the inhalers.  

So if there is anyone here with knowledge of old school pharmaceuticals, or better yet someone that used these back in the day who could enlighten me it would be greatly appreciated.  Thanks in advance-pld


----------



## fryingsquirrel

65 mgs.


----------



## peacelovedope

If only those things were still around...


----------



## hobhead

Usually once was enough when we young shitheads broke open the Vicks Inhalers and scarfed down the cellulosic filler that contained the low rent, amphetamine load .
One could look forward to belching menthol laden stomach fumes and chattering on and on for hours upon hours--One time was a cure. 
Greenwich Village prior to '63 was not a place where reason was struck.


----------



## LivingOnValium

It was 250mg racemic amphetamine base.

It's a really high dose for beginners especially.

That's equivalent to 125mg d-amphetamine.


----------



## /navarone/

*So i was pondering about this substance......plz forgive me if its effing stupid.*

Gday mates.

After reading some pikhail, wikipedia and obviosuly bluelight i was pondering on this stubstance.

Before tho i would like to ask....what are th advantages and disadvatages of phenylisobutylamine compared to amphetamine (reminder, i already know it has weaker dopaminergic functions).

So after combining many hypothesis, the three aphenylethylamine substances that came into my mind are:

1:





2:





3:





I all ear for any crit5ics so please feel fre to unleash your pharmacologically sadistic blashing if you will.


----------



## fryingsquirrel

I saw that picture, the one from which I got the 65 mg figure was on the same page. It looked more like a modern inhaler. I assume the dosage was lowered over time.


----------



## Torabora

yea well but when you inhale once you wont get 250mg out of it? that would kill a lot of people ^^

I think it worked more like a nosespray?


----------



## Vader

^That was the intended use, but they were abused by cracking open the inhaler and swallowing the lot.


----------



## theotherside

What year did they swith to using propylhexedrine j.o.c.?


----------



## nuke

q answered, merged with the big thread.


----------



## nuke

/navarone/ said:


> Gday mates.
> 
> After reading some pikhail, wikipedia and obviosuly bluelight i was pondering on this stubstance.
> 
> Before tho i would like to ask....what are th advantages and disadvatages of phenylisobutylamine compared to amphetamine (reminder, i already know it has weaker dopaminergic functions).
> 
> So after combining many hypothesis, the three aphenylethylamine substances that came into my mind are:
> 
> I all ear for any crit5ics so please feel fre to unleash your pharmacologically sadistic blashing if you will.



Not really advanced, merging with the big questions thread..


----------



## peacelovedope

theotherside26 said:


> What year did they swith to using propylhexedrine j.o.c.?



I believe it was either after the Controlled Substance Act was passed, or when amphetamine was moved from schedule III to II. So early so 1970 or within a few years of it.


----------



## Phener

*25B-NBOMe (minus amine) speculation*

Ok so we know it's possible with Methylphenidate:

From methylphenidate:
http://en.wikipedia.org/wiki/Methylphenidate
you can then get 0-2172:
http://en.wikipedia.org/wiki/O-2172
which is completely devoid of a nitrogen. 

SO considering the UBER potency of 25B-NBOMe (http://en.wikipedia.org/wiki/25B-NBOMe) could there be some replacement that would simulate the nitrogen effectively enough to keep the steric structure in place?? Hence being COMPLETELY DEVOID of ANY controlled drugs regulations anywhere! wahoo :D


----------



## nuke

Probably not, since the nitrogen seems to be necessary for an essential basic hydrogen-bonding interaction.  The ether might be active but it's a poor hydrogen bonding partner, and you wouldn't want to eat the phosphorus homologue due to toxicity.


----------



## MurphyClox

...shit, my post was deleted because I was writing while Nuke moved Phener's post to this thread. Anyway, again in short:

According to _Grimm's law of hydride_ shift does an atom - by addition of n protons - obtain the properties of the element that is n positions further in the periodic system of elements, i.e.:

1. F = OH = NH2 = CH3
2. O = NH = CH2
3. N = CH​
It's a very simple rule, valid for the sterical comparison (read: bioisosterical) of certain moieties. Obviously, it does not pay attention to acid/base-properties or present lone electron pairs.
Nonetheless could one accordingly substitute the secondary amine in the NBOMe's with either an ether-oxygen or simply with a methylene-bridge. I doubt that any of these variations will show activity comparable to the parent compound. The nitrogen seems to be required for receptor binding.

Peace! - _Murphy_


Edit: To my knowledge, a bioisosteric replacement as described above was not tried yet by anyone.


----------



## nuke

Sorry Murphy!


----------



## MurphyClox

No prob! Happens...


----------



## pharmakos

lots of chemicals form crystalline structures under the right conditions.

do drugs form crystals (pseudo-crystals?) on our receptors?


----------



## MurphyClox

^A crystal is defined as a body made up of repeating patterns. As the usual stochiometry is something like 1 receptor per 1 to a few ligands, one can't speak of a pattern here, but just single instances of molecular interaction.

Therefore, the answer is: No.

And please enlighten me what the term "pseudo-crystal" is referring to.


Peace! - _Murphy_


----------



## pharmakos

MurphyClox said:


> ^A crystal is defined as a body made up of repeating patterns. As the usual stochiometry is something like 1 receptor per 1 to a few ligands, one can't speak of a pattern here, but just single instances of molecular interaction.
> 
> Therefore, the answer is: No.
> 
> And please enlighten me what the term "pseudo-crystal" is referring to.
> 
> 
> Peace! - _Murphy_



i was thinking that since these chemicals tend to cohere they might actually end up forming structures on our receptors.  perhaps different crystalline shapes cause different reactions.  don't all the best drugs produce the prettiest crystals in the laboratory?  

oh, p.s. "pseudo-crystal" is what i would call a crystal in its infancy... a nucleus that would form a crystal under different circumstances.


----------



## MurphyClox

You are totally confusing the definition of a 'crystal'. Your last response doesn't make any sense.

- _Murphy_


----------



## /navarone/

nuke said:


> Not really advanced, merging with the big questions thread..



Neways what would be you opinion on those 3 molecules I proposed?


----------



## dread

Hey everyone. What are your opinions on this molecule I'm proposing?

It looks so nice and symmetric, I just had to post it here.


----------



## Astavats

^That sums up things nicely lol


----------



## MurphyClox

^DREAD! Aweeeesome shit 
How do you name it? May I suggest something like Dreadaine...or no, BETTER: Benzene! YES! Holy, I'm genius. Goddamnit. Fuck Kekulé!


----------



## dread

Well I'm still not satisfied, so I think I'm going to add a methylenedioxy or two to make it even _awesomer_.


----------



## P A

Does dextroamphetamine (and its many DAR/NER cousins) significantly elevate extracellular levels of serotonin in clinically used dosages?


----------



## dread

Would the malonate ester of psilocin form zwitterions?


----------



## MurphyClox

dread said:


> Would the malonate ester of psilocin form zwitterions?


Did I get it right: Esterify the phenolic OH with malonic acid, while leaving malonic acid's 2nd COOH untouched?!
Then the answer would most probably be: Yes, zwitterionic structure is expected.

- _Murphy_


----------



## dread

MurphyClox said:


> Did I get it right: Esterify the phenolic OH with malonic acid, while leaving malonic acid's 2nd COOH untouched?!
> Then the answer would most probably be: Yes, zwitterionic structure is expected.
> 
> - _Murphy_



Yes you got it right and thanks for the answer. 

Next I'm wondering how this would affect the stability & pharmacodynamics of the compound... but I guess there's no real answer for that...


----------



## Astavats

Can anyone give me binding affinity/data of atropine, hyoscyamine, or scopolamine on any opioid receptor subtypes (mu/kappa/delta)? I'm sure it's to a quite negligible extent but if it's been published I want to see it. I'd appreciate any help.

All the best.


----------



## pharmakos

thenightwatch said:


> i was thinking that since these chemicals tend to cohere they might actually end up forming structures on our receptors.  perhaps different crystalline shapes cause different reactions.  don't all the best drugs produce the prettiest crystals in the laboratory?
> 
> oh, p.s. "pseudo-crystal" is what i would call a crystal in its infancy... a nucleus that would form a crystal under different circumstances.



okay, perhaps this is a better way to put the abstract concept that's in my head into words.....


2C-I, for instance, likes to form crystals, no?  crystals aren't too key to the concept... all that's necessary for this idea is the knowledge that 2C-I molecules tend to stick to each other.

we're (fairly?) sure that one 2C-I molecule will bind to one spot on one 5HT receptor, right?

well, will other 2C-I molecules stick to that one molecule that's stuck to the receptor?


----------



## MurphyClox

Ahhhh, now I get what you mean. 

The answer is NO, several 2C-X-molecules won't stick together in solution, and we are talking about solution only.
On the one hand are crystals of 2C-X not stable in an aqueous environment. Consequence: They dissolve when water hits them. Sounds trivial, but it isn't. Remember that there are numerous compounds whose crystals are stable (read: insoluble ) in water, e.g. barium sulfate.
On the other hand - even if 2C-X-crystals would be insoluble in water - does it take more than two or three molecules of the same kind to gain of the stabilizing properties of a crystalline structure.


Peace! - _Murphy_


----------



## Imperial Tacohead

This is probably a silly question, but I'm curious.  Reading about the various uses of coca teabags, I've seen several people describe a method whereby they stick a bag in their mouths to chew or suckle, along with a bit of baking soda to "activate" the alkaloids.  What does "activate" mean in this context?  And why don't I read about people adding baking soda to their tea for the same purpose?


----------



## MurphyClox

When chewing this stuff people are trying to absorb the active ingredients through the mouth's mucosa. For this you need the freebase form (lipophilic), which is liberated by the action of a base (=soda).

When drinking the tea, you want the ingredients to be in the form of salts, because these are more water-soluble. The alkaline pH of the small intestines turns them into the freebase form, ready for absorption.


- _Murphy_


----------



## P A

> Can anyone give me binding affinity/data of atropine, hyoscyamine, or scopolamine on any opioid receptor subtypes



I've done plenty of reading on scopolamine and its derivatives, mostly as it relates to CNS actions, not pharmacochemistry, but to my limited knowledge, if the Devil's Breath has any affinity for opioid subtypes, it's most likely clinically and recreationally negligible.

Wish I could help definitively, but I have to warn you - don't get your hopes up for any decisive responses. I've asked a few questions here regarding pharmacophoric binding profiles before, and have been fully ignored. Pretty disappointing (and surprising), given the title "Advanced Drug Discussion," but apparently these boards are occupied mostly by little more than bored theoretical drug chemists without extensive access to pharm data.


----------



## Astavats

Thanks for your response P A, I don't disagree with you about ADD but rather blame the  "not-so Advanced" threads going around. The "what about this hybrid molecule...by the way I have no basis SAR or reasoning" or "silly named compound by vendor" threads aren't helping.

The reason I ask is a long story, but in short curiosity and to prove something to someone.


----------



## MurphyClox

^In contrary to the pathetic babble of *P A*, the reason why nobody answered to your question could simply be that nobody knows the answer. 

I'm neither bored nor do I not have extensive access to 'pharm data'. Actually, my access is quite extended. But - like most others here - do I have to set priorities and can not spend hours for searching some minor information for somebody I hardly know. Anyway, I made an exception and spend some hours (well, 2, to be exact) in search for an answer. And the answer is (as said above): We simply don't know.

I couldn't find a single hint that the binding of either atropine (resp. hyoscyamine) or scopolamine at the opioid-receptors was studied at any time. Both are well known and described in detail as muscarinergic ligands, but that's it so far.

A single source - albeit unreliable - states a Ki of 16200 for atropine; unit not given (haha), but it's nM I assume. Hot ligand was naloxone. Receptor-subtype is stated as "mainly µ-type" (LOL!). But as I said: The source is highly unreliable (European patent No. 289070 from *1988*).


Peace! - _Murphy_


----------



## MurphyClox

An own question this time:

Can somebody comment on the biological activity of "ICP" (1-(3-indolyl)-1-phenylcyclohexane), i.e. the indol-3-yl-analogue to PCP?

Active? Subjective effects?


Thanks in advance!

- _Murphy_


----------



## RGB

As far as binding affinities go, why not take a look at something like the PDSP Ki database rather than asking someone to do the grunt work of looking up your stuff for you? If that's not working out for you, there's a stickied list of helpful resources that you could try, too.

I don't pretend to know a lot about chemistry, but I imagine that the information you're looking for is either going to be published in a paper somewhere (and thus accessible via one of these binding affinity databases), or you'll have to do the assay yourself. I doubt there's some secret database of 'pharm data' privy to only certain individuals. If there were, I doubt they'd be allowed to leak information from it in any case.


----------



## Astavats

Thank you Murphy, I appreciate it. I was afraid there would be no data/research on it so I'll gladly take this much you've dug up.



RGB said:


> As far as binding affinities go, why not take a look at something like the PDSP Ki database rather than asking someone to do the grunt work of looking up your stuff for you? If that's not working out for you, there's a stickied list of helpful resources that you could try, too.



If this is in response to my post, then for the reason I was not aware of these sources. I've done the 'grunt work' myself searching and found nothing so I figured I would ask others who know more for help. I'm here to learn and nothing else. If this was not directed at me please overlook this.


----------



## RGB

On rereading my post, I realize that I came off as being a bit more caustic than I'd intended -- sorry about that. 

The post wasn't directed at you specifically, more at the problem that you and P A were discussing of not being able to find binding affinities. Also, you're welcome.  That database I mentioned is unfortunately pretty poorly normalized; things go by strange names and there are multiple apparently identical entries in some of the drop-down fields. I'm sure there are better ones out there.


----------



## Astavats

Understandable, no worries. Any direction at my beginner level pharma/chem intellect is always a helpful one. Going to check out your suggestions now. All the best!


----------



## MurphyClox

With regard to the 'grunt work' I can recommend one of ADD's finest threads, List of free chemistry databases.

It's totally undervalued (why the heck?!) but it's frequent usage would spare us a lot of useless threads at ADD.

Nonetheless, Astavats' question turned out to be quite tricky to answer. So, no prob pal, it was a pleasure to help out (even if the answer was disappointing).
I just detest such snobbish attitudes about so-called "bored theoretical drug chemists without extensive access to pharm data". Some folks are working their ass off to give this forum a meaning 

- _Murphy_


----------



## seep

RGB said:


> I doubt there's some secret database of 'pharm data' privy to only certain individuals. If there were, I doubt they'd be allowed to leak information from it in any case.



There are indeed secret databases: proprietary data out there that hasn't been published; some of it'll not be published anytime soon.  Questions come up on this board every once in a while that I know the answer to but that I won't answer cuz there'd be a trail of crumbs.  And I'm an absolute nobody, with no credentials to speak of and really not much to lose.

So imagine the amount of data that the posters here who have or will soon become credentialed and trusted professionals in the pharm industry--imagine the amount of very specific info they're privy to. Imagine a Pharm-D for Merck!

The utopia P A pines for is untenable.


----------



## atara

MurphyClox said:


> An own question this time:
> 
> Can somebody comment on the biological activity of "ICP" (1-(3-indolyl)-1-phenylcyclohexane), i.e. the indol-3-yl-analogue to PCP?
> 
> Active? Subjective effects?
> 
> 
> Thanks in advance!
> 
> - _Murphy_



I spend the last half hour searching and I have no reason to believe any such compound has ever been synthesized. However, if you're a chemist looking to make an indolic dissociative, you may find this paper interesting...

http://www.scribd.com/doc/35753990/indolenmdaantagonists


----------



## MurphyClox

^Nope, I'm not interested in the synthesis but just the activity of this derivative.



atara said:


> I spend the last half hour searching and I have no reason to believe any such compound has ever been synthesized...


...which seems to be true. Looks indeed novel.

Thanks for your help anyway! 

- _Murph_


----------



## P A

> the reason why nobody answered to your question could simply be that nobody knows the answer



No shit. In what way is this contrary to my 'pathetic babble?' I'd assume that in all likelihood, someone _does_ know the answer, just not someone who happens to post on Bluelight.ru.



> Anyway, I made an exception and spend some hours (well, 2, to be exact) in search for an answer



>extensive access
>it took you two hours

yeahokaysureman



> snobbish attitudes



No need to get so personally butthurt about a generalized comment regarding the apparently predominate userbase of a specific forum on a website full of discussion boards. What I said wasn't directed at anyone in particular, and was just expressing mild frustration at being ignored by a group, _not _ you or anyone in particular. And where I come from, calling someone a chemist [or even a bored one, at that] isn't an insult. And assuming that others didn't have any higher level access than I did obviously wasn't intended as deprecating - though I'm not sure how such an observation, whether misplaced or not, could be seen as offensive by any stretch of the imagination - unless you think I was concomitantly "snobbishly" insulting myself, as I transparently present myself as having no higher-level access (journals, Medline, etc.) whatsoever. Either way, go fuck yourself.

Also, as an example, dextromethorphan/dextrorphan aren't exactly obscure drugs - for anyone with slightly more access to published literature than myself, finding the Ki data should be relatively easy, and shouldn't take long at all [definitely not "hours"]. Not to say that anyone owes me a damn thing, but it's not like I was asking for much. And believe me, using what little I had available, I _did _ look. At a lot. For a good while. I would only ever ask such a question on a website like this as a last ditch attempt, because I don't particularly like bothering people with minutiae trivia and asking them to do a service I should be able to adequately perform myself. I usually only ask when the topic in question is of proximal importance to me or someone else. To repeat the example, while I was already curious about DXM/DXO's relative affinities, I was actually more interested in whether popular concerns regarding serotonin syndrome were warranted, and whether a friend of mine had put himself at considerable risk. I only asked after combing Google Scholar for an hour and poking around elsewhere, all of which resulted in jack shit. Being ignored while others' questions were promptly answered was annoying, and I said so, very mildly - chalking it up not to incompetence or anything personal, but to a discrepancy in fields of interest and widespread lack of access to pharm jounals [which for a layman is completely understandable]. That doesn't warrant bristling up and being a righteous prick about it.



> The utopia P A pines for is untenable.



And what utopia is that? None of the questions I've asked on this board are anywhere near the academic level to which you refer, and the with the advent of the intarwebs, the majority of basic pharmaclogic data is nowadays pretty transparent, even to the general public. DXO's binding affinities? Amphetamine's mechanism(s) of action? I've read many publicly accessible abstracts of published studies directly related to those topics, a few of which hint at containing plenty of detailed data _in the fulltext_ to which I don't always have access. My questions aren't wildly speculative or avant-garde, and secret databases be damned. seep, I appreciate the anecdote on the dark curtains and bread crumbs [a truth I can't deny], but I think that's hardly relevant to me or the questions _I've_ asked, in this thread or in the past. Like I said, I don't think I'm asking about something completely obscure, then puling when rebuked, as Murphy and you would have it.


----------



## P A

> As far as binding affinities go, why not take a look at something like the PDSP Ki database rather than asking someone to do the grunt work of looking up your stuff for you? If that's not working out for you, there's a stickied list of helpful resources that you could try, too.



If I had known about this in the first place, I might never have needed to ask. Thank you for pointing me in the right direction. And for the record, I try to answer as many questions as I ask, and do 99% of my own research (UTFSEing and such). I don't make it my life's mission to burden everyone else with 'grunt work.'



> Astavats' question turned out to be quite tricky to answer



Mine, on the other hand, were just ignored.



> Some folks are working their ass off to give this forum a meaning



Heroes like you, amiright Murph? I think you've adequately made your point. You can get off your self-important soapbox now. 

Thanks for nothing, asshole.


----------



## vecktor

^ rather than getting pissy with each other in public take it to PM.

As for amphetamine action there are several academic review papers on the topic one I think is publically accessable, I vaguely remember posting links to one. 

A more general point is that for a question to be answered it has to excite some interest in those offering the answer because usually it involves doing some research, if it doesn't excite any interest you are not going to get any answer, additionally a lot of folks do the calculation and if it looks like the exchange of information is going to be completely one sided then it is unlikely to be worth the effort.

AMPs activity is mostly synaptic MAT reversal, VMAT inhibition and weak amine effect on the vesicles.


----------



## P A

> A more general point is that for a question to be answered it has to excite some interest in those offering the answer because usually it involves doing some research, if it doesn't excite any interest you are not going to get any answer



Well sure. But one would think that at least one other individual posting on a board called Advanced Drug Discussion would have some degree of intrinsic interest in discussing a specific drug on an advanced level. Aside from the admittedly boring question regarding binding affinities (the kind of question I typically shy away from asking if I can avoid it), how do my questions substantially differ from those of the "hay guise look kewl molecule" crowd? Both rely near-entirely upon intrinsic fascination and self-driven academic interest as motivation for collectively arriving at a satisfying answer. Probing deeper into amphetamine's mechanism than "it reverses the transporter, VMAT, so on and so forth" opens an array of topics for higher-level discussion for those genuinely interested, some which I directly invoked within the post in question. If you actually read my original post, I doubt you'd feel the need to introduce me to basic rules of human conversation.


----------



## vecktor

just in case you take it the wrong way my earlier post is not a personal criticism but an observation

in an ideal world questions would all get answered everyone would have access to the literature and the ability to understand the literature,That may be how it should be, but it is not how it IS. most people don't have enough time.

I did a quick google search and found http://www.lycaeum.org/research/researchpdfs/1998_kankaanpaa_1.pdf

guess what.... it describes the alterations in extracellular SE in rats, now if you had linked to that in your question and asked what correlation did it have to therapeutic or recreation amp or meth doses then that would have suggested that you had something to add....


----------



## vecktor

P A said:


> Well sure. But one would think that at least one other individual posting on a board called Advanced Drug Discussion would have some degree of intrinsic interest in discussing a specific drug on an advanced level. Aside from the admittedly boring question regarding binding affinities (the kind of question I typically shy away from asking if I can avoid it), how do my questions substantially differ from those of the "hay guise look kewl molecule" crowd? Both rely near-entirely upon intrinsic fascination and self-driven academic interest as motivation for collectively arriving at a satisfying answer. Probing deeper into amphetamine's mechanism than "it reverses the transporter, VMAT, so on and so forth" opens an array of topics for higher-level discussion for those genuinely interested, some which I directly invoked within the post in question. If you actually read my original post, I doubt you'd feel the need to introduce me to basic rules of human conversation.



I have next to no interest in AMP whatsoever even on an academic discussion level, the basic mechanisms have already been discovered and discussed on these very forums, IMHO it really isn't that interesting. I don't need a grand unified theory of speed.

and don't claim to have looked for the open information, you clearly haven't, I found this in 5 minutes through google scholar.

http://sulzerlab.org/pdf_articles/Sulzer05AMPHreview.pdf


----------



## P A

> I have next to no interest in AMP whatsoever even on an academic discussion level, the basic mechanisms have already been discovered and discussed on these very forums, IMHO it really isn't that interesting. I don't need a grand unified theory of speed.



And that's just fine.



> in an ideal world questions would all get answered everyone would have access to the literature and the ability to understand the literature,That may be how it should be, but it is not how it IS. most people don't have enough time.



I'm aware of this.



> guess what.... it describes the alterations in extracellular SE in rats, now if you had linked to that in your question and asked what correlation did it have to therapeutic or recreation amp or meth doses then that would have suggested that you had something to add....



I've read that paper twice before.

And I think it was pretty clearly implied in context that I _knew _
that amphetamine did increase serotonin efflux at some massive IV dose in rodents (due to its comparatively low affinity for the SERT or whatever). I assumed that since this was ADD, tidbits like that would essentially be common knowledge among those toward whom the question was directed in the first place. This is why I specified human *clinical * dosages in the question, thereby providing a hint of purpose and utility for both the question and answer. I believe I've met my burden.



> and don't claim to have looked for the open information, you clearly haven't, I found this in 5 minutes through google scholar.



I have. And of all the (literally) thousands of times I've visited Scholar, I've never once come upon any PDF or abstract on "sulzerlab.org." And yeah, I've read the abstract for that exact study dozens of times on Elsevier and its ilk, and have never been able to find the fulltext. Last time - and every time - I checked Scholar and elsewhere (and I've scoured dozens times, and like everyone else, don't have time to do so every day), a fulltext was not available for public access outside of paid subscription, something I can't afford. Either something's dramatically changed since my last search, or you didn't just 'find it.' You probably found the abstract, then used "sulzerlab" to get the fulltext, or something to that effect. Either way, thanks.


----------



## P A

I stand corrected on that. I just did a Scholar search using 'amphetamine mechanism release' as a query to find that exact study, and came up with only one link to the study you posted, the PDF link for which is worthless to me (and, by the way, is new - it wasn't there every time I searched before). My computer refuses to load from "designfiles.org," which is where I'm guessing you got the full paper. All apologies for the negligence.


----------



## vecktor

the question regarding clinical recreational doses can also be answered without using hidden literature, it just requires you to work it out.

from the lycaeum paper regarding AMP, there is an effect on extracellular serotonin at 9mg/kg rat, and a very slight effect at 3mg/kg rat, using the BSA correction factor (shown as you obviously know because you will have read the literature) to correlate to variations interspecies doses rat human conversion is 1/6 so the 9mg/kg is 1.5mg kg human, ie HED of >90mg  3mg is 30mg  so the short answer is at clinical doses this study would indicate there is little or no effect on extracellular SE. 

I don't ask many questions on forums, because I can usually find out the answer myself. In general the answers are all out there in the public domain, it requires a decent searching strategy and enough background knowledge to sort the wheat from the chaff.  Having full literature access is nice, sure, but often it is quicker to use open access stuff. for example scholar gives you the abstracts, then web search for the file name or author and often the paper is available. IME Scholar usually beats scopus crossref and other closed literature searches. once you have a decent starting paper, it is then the old library technique of looking up the cited papers both backwards and forwards.  I don't buy it when people come on these forums, say they have looked but don't cite the papers they have found even the abstracts are helpful. like I said earlier information exchange has to be mutually beneficial to work, someone with time but without full literature access can help someone with no time but full access by finding the interesting abstracts.

The sulzer AMP mechanisms paper has been available open access for a long time, I am certain I have linked to it in previous posts.


----------



## UYI

Any information available regarding:

5-Methylbutylone / 1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethylamino)butan-1-one

Could anyone post a structure of this chemical please?


----------



## MurphyClox




----------



## UYI

Just to let people know that this is now being produced as a replacement for the recently banned in the uk - Butylone, cant find any information for this anywhere.


----------



## P A

> the question regarding clinical recreational doses can also be answered without using hidden literature, it just requires you to work it out.





> interspecies doses rat human conversion



I never appealed to any "hidden literature." And, obviously, I would be far more interested human data (were it available). Which I couldn't easily find. Which is why I asked. [And yeah, yeah, I know, amphetamine releasing agents are very similar in effect from rodent to primate, but I found some conflicting and/or ambiguous results - as in, I didn't just read one study like you did - and figured I'd ask directly]. 

And seriously man, I already apologized for any personal negligence [not that I really believe there was any egregious amount in the first place]. What the fuck more do you want?



> I don't buy it when people come on these forums, say they have looked but don't cite the papers they have found even the abstracts are helpful.



Even if that sentence were fully intelligible, I'm not sure how much I could get out of it. You don't buy it? What, do you think I'm lying or something? Fucking ridiculous. To the same extent that many people don't have time to dig up little scraps of information for every patron of these boards all of the time, I'm not going to spend my day _re_-digging up information and _re_-hunting for abstracts after I've already searched for quite a while for what amounts to little more than a redundant formality. I articulated my questions crisply and unambiguously - what purpose could one abstract related to the topic serve? To repeat: the crowd toward whom the question was directed in the first place obviously wouldn't need a cited abstract within the question in order to discuss a possible (or *the*) answer. Though I had in fact read both of the abstracts to the studies you posted, I'd also read countless others. Should I have posted those as well? Or is that even what you meant 'even abstracts are helpful?' I'm not necessarily looking for fulltext papers and inline citations, just answers and discussion, like [I think] everyone else here.

And yeah, I'm fully aware of how to use Google Scholar and perform low-level academic research on the internet, as I've been doing this for quite a while; thanks.



> The sulzer AMP mechanisms paper has been available open access for a long time, I am certain I have linked to it in previous posts.



Like I already said in the above post, before the other day, I had never searched Google for that _particular _ paper, and my computer refuses to open the "designfiles" PDF link on Scholar. Mother of christ.

And what's with this bizarre undertone of condescension? "_The reason you don't ask many questions_?" *I* don't ask many questions, because, like you, I typically find the answers myself. You're a mod, so I'm sure you're more than capable of looking over all of my posts - in almost two years of being a member of this site, the only direct, academic questions I've ever posed are to be found in this sticky. Making for a total, if I remember, of four or five. Every other question I've ever asked has either been purely non-academic, fully pertinent to an ongoing in-thread discussion, and/or introduced in order to open a thread for conversation, clearly presented and phrased as such. Why is this such an issue for you? Though I had to acquire the skill on my own, I'm fully competent at hunting for open-access data, and I'll be damned if I'm going to be accosted and chided for a fault I don't have. You picked two examples of what you apparently take to be unnecessary questions - the one example was poor, for reasons I explained; the other was simply a matter of glossing over one link [that I either had forgotten about over my many searches or had never seen before] to a fulltext that my computer wouldn't even open. And, as I've already acknowledged my 'mistake' and apologized in embarrassment [as if that was even called for in the first place], why do you continue to push the issue?


----------



## vecktor

UYI said:


> Just to let people know that this is now being produced as a replacement for the recently banned in the uk - Butylone, cant find any information for this anywhere.



It would appear that this is also covered by the generic cathinone ban in the UK, not that selling something illegal has stopped the vendors in the past


----------



## vecktor

P A said:


> What the fuck more do you want?



From you? nothing. 

You seem to think that I am criticizing you personally, I'm not I am merely observing that the answers you seek are already out there for anyone to find.


----------



## P A

> I am merely observing that the answers you seek are already out there for anyone to find.



Thanks for the observation.


----------



## Imperial Tacohead

I'm not sure whether this deserves its own thread, so I'll try here first.  I've recently become a big fan of 2-fluoroamphetamine.  Unfortunately, 2-FA is by far the most obscure RC that I've tried, and there seems to be a real dearth of good information online about potential health risks.  I seem to remember reading in a few places that the fluoroamphetamines in general were surprisingly lacking in neurotoxicity, but what other pitfalls should I be looking out for?


----------



## jaguraguguru

UYI said:


> Any information available regarding:
> 
> 5-Methylbutylone / 1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethylamino)butan-1-one
> 
> Could anyone post a structure of this chemical please?



That's weird. 1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethylamino)butan-1-one is not 5-methylbutylone, it's n-methylbutylone. 5-methylbutylone is:


----------



## seep

jaguraguguru said:


> That's weird. 1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethylamino)butan-1-one is not 5-methylbutylone, it's n-methylbutylone. 5-methylbutylone is:



No. That's 7-methyl butylone.


----------



## dread

5-methylbutylone is in fact impossible since the side chain is already in the 5-position.


-- 

on another note,

http://en.wikipedia.org/wiki/Calcium_morphenate

How does morphine form a salt with calcium? Aren't they both bases?


----------



## MurphyClox

I guess calcium morphenate is based on the phenol's acidity (pKs ca. 10).

- _Murphy_


----------



## dread

MurphyClox said:


> I guess calcium morphenate is based on the phenol's acidity (pKs ca. 10).
> 
> - _Murphy_



But of course! Should have thought of that...

cheers murph


----------



## dread

Could the n-phenyl-propionanilide in fentanyl be replaced with a benzoyl group while retaining mu-agonist activity?

ie. n-phenethyl-4-benzoylpiperidine.


----------



## MurphyClox

Very unlikely that opioid activity will be remained.

But your suggested compound is a reported 5HT2A-antagonist (a reduced version of ketanserine), Ki = 9.6 +/- 3.6 nM.
Ref: Glennon et al: _J Med Chem_ *1995*, 38(7), p.1196.


YO! - _Murphy_


----------



## dread

MurphyClox said:


> Very unlikely that opioid activity will be remained.
> 
> But your suggested compound is a reported 5HT2A-antagonist (a reduced version of ketanserine), Ki = 9.6 +/- 3.6 nM.
> Ref: Glennon et al: _J Med Chem_ *1995*, 38(7), p.1196.
> 
> 
> YO! - _Murphy_



Interesting. Thanks again murphy!


----------



## shake

ppl of advanced drugs i just wanted to take the time to invite yall down to my section of bluelight. we have an amazing group of ppl down there and many light hearted and serious discussion threads about the social aspects of drugs along with current trends. iam taking the time this morning to visit each forum on BL to give everyone a hardy welcome and join us. so remember north & south america drug discussion & social, long name awesome group of ppl.

hope to see yall around


----------



## Xynthetic

I understand that inhibition prevents re-uptake causing less transmitters to leave the synaptic cleft and I'd like to guess that releasing of transmitters would occur through a transporter to the synapses. Both of these events increase the amount of a designated neurotransmitter's activity over a period of time, but what are their important differences?

E.G.: comparison of methylphenidate (inhibitor) to amphetamine (releaser)


----------



## seep

dread said:


> http://en.wikipedia.org/wiki/Calcium_morphenate
> 
> How does morphine form a salt with calcium? Aren't they both bases?



The salt is used to extract morphine from the dissolved opium latex? This is what I was trying to do with another base in my (failed) voacangine extraction project (thanx Vektor: I was too discouraged to respond to your post a couple months ago).

As long as the pH of the solution is higher than the pKa of the *protonated* amine, the amine will not abstract protons from the solution.  After that, what Murphy said.

Question: what's the pKb of carbonate (the *diprotonated* conjugate base of carbonic acid)?  I confess I am in a depressive funk right now and have forgotten how to look up pKb's of conjugate bases of weak diprotic acids.


----------



## Help me please

*morphine sulfate IR v. norco 10/325 mg*

http://www.bluelight.ru/vb/showthread.php?t=520656

I posted my question in TDS but was told maybe someone here could answer it.

Was wondering if I can use norco when I run out of the morphine sulfate IR 15 mg pills for my taper. I have a bunch of those left and am avoiding going back to the PM dr if possible. No reason other than I figure to be off all opiates mid September at the latest and just trying to save the time spent dealing with an appointment.

I only take the MS IR every 8 hours. Currently at 22.5mg, 7.5 mg, 30 mg. A bit more than a week ago I was at 30, 30, 30 and Doctor wanted me to taper to 15, 15, 15 this week. Went through bad WD's in July and don't want to go there again. For the record I am taking myself off the meds and the dr thinks I need to remain on them.


----------



## smackem

Yea. easily. Take one hydro everyone 8 hours, then just taper.


----------



## Help me please

smackem said:


> Yea. easily. Take one hydro everyone 8 hours, then just taper.



I'm unclear. You say take one norco every 8 hours but once I am at what morphine dose? If I did that at any but my 4 pm, 7.5 mg dose now I would go into WD.


----------



## LawnChairSkank

Help me please said:


> I'm unclear. You say take one norco every 8 hours but once I am at what morphine dose? If I did that at any but my 4 pm, 7.5 mg dose now I would go into WD.



Hydrocodone has about the same oral potency as morphine. Just stick to your tapering schedule when you switch to the norcos. Good luck man.


----------



## smackem

15mg of oral morphine sulfate is about 10mg of hydrocodone and might even be a bit less.

So one 15mg morphine pill = 1 10mg hydro pill.

Just start taking less and less of the hydros....


----------



## smackem

I am pretty sure hydro is stronger on a mg per mg basis than morph sulfate. I know I would rather have 100mg of hydro than 100mg of oral morphine. IV morphine is a different animal, as we all know..


----------



## Help me please

LawnChairSkank said:


> Hydrocodone has about the same oral potency as morphine. Just stick to your tapering schedule when you switch to the norcos. Good luck man.



Thank you. I do wonder whether once I am that low if it will matter at all. I mean I will have to cut the norcos in 1/4's and which takes me to 2.5 mg doses. The MS IR was to drop to 3.75 mg doses at some point. Maybe when I get to the 3.5 on the morphine I can just go to half a norco and see from there. It would be easier to do that in the long run...maybe


----------



## Help me please

smackem said:


> 15mg of oral morphine sulfate is about 10mg of hydrocodone and might even be a bit less.
> 
> So one 15mg morphine pill = 1 10mg hydro pill.
> 
> Just start taking less and less of the hydros....



Wow, I am hearing two totally different opinions on the m v n issue. I will call my pharmacist in the morning to make sure. I need to do a pill count too and see how the new taper schedule adds up. I am tapering less mg-wise but more often too. I'm tired and confusing myself let alone all you guys 

Thanks


----------



## MurphyClox

seep said:


> Question: what's the pKb of carbonate (the *diprotonated* conjugate base of carbonic acid)?  I confess I am in a depressive funk right now and have forgotten how to look up pKb's of conjugate bases of weak diprotic acids.


1st deprotonation:
H2CO3 + H2O ---> HCO3-  +  H3O+
pKa = 3.88; But because the equilibrium CO2 + H2O -> H2CO3 lies very much on the left side (H2CO3 is unstable!), the first equation and the hydrolysis are usually combined to give a pKa = 6.5

2nd deprotonation:
HCO3- + H2O ---> carbonate + H3O+
pKa = 10.33

The relation between pKa & pKb is as follows:
pka + pkb = 14


Peace! - _Murphy_


----------



## seep

^Thanks. That always confuses me: acids and bases that are prone to decomposition.


----------



## Druidus

*Extraction of DMT*

I thought this was ok because it isn'tabout synthing anything.

In the extraction of DMT, is there anything that you can use other than pure ammonia to do it?  I can't seem to find any of the commonly listed strong bases.

Could I use urea? If so, how?  Cold I get my own ammonia from urine?  How would I purify it?  Just some suggestions I got.


----------



## atara

Urea is not a base.

http://lmgtfy.com/?q=STB+DMT+extraction


----------



## mmarty

Is ammonia that hard to find?


----------



## Druidus

It is very hard to find here, at least in pure form.


----------



## atara

Druidus said:


> It is very hard to find here, at least in pure form.



That's because anhydrous ammonia is a gas. I'd suggest looking for a simpler tek; they don't all require annie.

If you're set on using anhydrous ammonia, you'll find several preparation methods in Rhodium's Archive.


----------



## Ylide

Can you find washing soda (sodium carbonate)?


----------



## MurphyClox

Ammonia gas can be easily produced from cheap ammonium salts and a suffiently strong base like NaOH or KOH. All OTC. Nonetheless is this not recommended to the layman, due to the hazard potential that this methods brings naturally.

- _Murphy_


----------



## dread

Druidus said:


> I thought this was ok because it isn'tabout synthing anything.
> 
> In the extraction of DMT, is there anything that you can use other than pure ammonia to do it?  I can't seem to find any of the commonly listed strong bases.
> 
> Could I use urea? If so, how?  Cold I get my own ammonia from urine?  How would I purify it?  Just some suggestions I got.



You can use pretty much any base for A/B, and any strong base for STB. 

I've had good results with KOH and NaOH. Sodium carbonate I tried a few times and it always gave me emulsions which were a bitch to deal with, so I don't recommend that.

If you have trouble finding bases, you can make wood ash lye: burn some wood, collect the ashes, soak in slowly boiling water - and you have a solution of wood ash lye. It is only useful for A/B though, won't work for STB.


e.- also, what are you using the ammonia for? If it's for purification, don't, the method of ammonia-purification is not recommended - it's a very outdated and inefficient method. Frankly, DMT extracted from MHRB shouldn't require any purification if done right - you should get a totally usable product without purifications or re-x:s.


----------



## (zonk)

*anyone know of N-Methyl-6-APB*

Anyone know whether these would be active/worthwhile

N-Methyl-6-APB
N-Methyl-6-APDB
N-Methyl-IAP


----------



## thescientist

*Are there oils which sink below water, and not rise above?*

I have heard sassafras may be heavier than water and lower instead of rise above the water.  Just wanted to see if anyone has some info on that one... 

thescientist


----------



## seep

a) Is it liquid at a temperature range at which water is also liquid?
b) Is it insoluble in water?
c) Is its specific gravity greater than 1?


----------



## thescientist

a. yes
b. yes
c. need hydrometer. coming soon.


----------



## fryingsquirrel

thescientist said:


> I have heard sassafras may be heavier than water and lower instead of rise above the water.  Just wanted to see if anyone has some info on that one...
> 
> thescientist


True. Google sassafras oil specific gravity


----------



## thescientist

Googled.  So this oil will actually be on the bottom? 
Interesting.


----------



## nuke

It's all about density, really.  Liquids with a larger density than water usually sink to the bottom if they are insoluble in water.


----------



## dread

I heard methylene chloride does this.


----------



## fryingsquirrel

(zonk) said:


> Anyone know whether these would be active/worthwhile
> 
> N-Methyl-6-APB
> N-Methyl-6-APDB
> N-Methyl-IAP


While I have no specific info, I find it very unlikely the first two wouldn't be active, and probably worthwhile as well. The third IDK.


----------



## Basic Base

i didn't even know it was possible to actually die from lsd OD.  wouldn't it more or less be from shock instead of the actual drug?


----------



## fryingsquirrel

Basic Base said:


> i didn't even know it was possible to actually die from lsd OD.  wouldn't it more or less be from shock instead of the actual drug?


Seems like I read somewhere that the only OD death from LSD was from a guy who IV'd a quarter gram in the mistaken belief it was meth. Oddly, I personally know someone who IV'd a similar amount of 2c-e under similar circumstances, but he lived. Had a look in his eyes like those pictures of guys from WWI who took artillery fire for six months, though.


----------



## seep

^re: lsd toxicity:



			
				Hofmann said:
			
		

> The toxicity of LSD has been determined in various animal species. A standard for the toxicity of a substance is the LD50, or the median lethal dose, that is, the dose with which 50 percent of the treated animals die. In general it fluctuates broadly, according to the animal species, and so it is with LSD. The LD50 for the mouse amounts to 50-60 mg/kg i.v. (that is, 50 to 60 thousandths of a gram of LSD per kilogram of animal weight upon injection of an LSD solution into the veins). In the rat the LDso drops to 16.5 mg/kg, and in rabbits to 0.3 mg/kg. One elephant given 0.297 g of LSD died after a few minutes. The weight of this animal was determined to be 5,000 kg, which corresponds to a lethal dose of 0.06 mg/kg (0.06 thousandths of a gram per kilogram of body weight). Because this involves only a single case, this value cannot be generalized, but we can at least deduce from it that the largest land animal reacts proportionally very sensitively to LSD, since the lethal dose in elephants must be some 1,000 times lower than in the mouse. Most animals die from a lethal dose of LSD by respiratory arrest.
> 
> The minute doses that cause death in animal experiments may give the impression that LSD is a very toxic substance. However, if one compares the lethal dose in animals with the effective dose in human beings, which is 0.0003-0.001 mg/kg (0.0003 to 0.001 thousandths of a gram per kilogram of body weight), this shows an extraordinarily low toxicity for LSD. Only a 300- to 600-fold overdose of LSD, compared to the lethal dose in rabbits, or fully a 50,000- to 100,000fold overdose, in comparison to the toxicity in the mouse, would have fatal results in human beings. These comparisons of relative toxicity are, to be sure, only understandable as estimates of orders of magnitude, for the determination of the therapeutic index (that is, the ratio between the effective and the lethal dose) is only meaningful within a given species. Such a procedure is not possible in this case because the lethal doge of LSD for humans is not known. To my knowledge, there have not as yet occurred any casualties that are a direct consequence of LSD poisoning. Numerous episodes of fatal consequences attributed to LSD ingestion have indeed been recorded, but these were accidents, even suicides, that may be attributed to the mentally disoriented condition of LSD intoxication. The danger of LSD lies not in its toxicity, but rather in the unpredictability of its psychic effects.



Erowid link with more about the elephant


----------



## fryingsquirrel

^That's awful. It did get me exploring the LSD vault at erowid again, and I found the report of the guy who shot LSD thinking it meth again. Turns out it was 320 mgs, more than they gave the elephant, FWIW.


----------



## Gup

dread said:


> I heard methylene chloride does this.



Yup.  Many halogen-containing oils are denser than water, and will sink.


----------



## WastedMuch

*Not sure if would work (New RC)*

I was wondering if this would work,

As Pcp Is Illegal but 3-MeO-Pcp isn't

So what about as mdma is illegal so could there be 3-MeO-Mdma

Thanks


----------



## dread

start here

http://en.wikipedia.org/wiki/Chemistry


----------



## Turing Machine

It depends on what you mean. The next carbon over from the para position can be numbered either as the 5 position or the 3 position. If you consider the methylenedioxy bridge to be at the 4,5 position it is a Pihkal comound MMDA and it is illegal in both the US and the UK. Also, 3-meo-pcp is not clearly legal in the US it could fall under the analog act. Prosecution is likely if sold for human consumption.

http://en.wikipedia.org/wiki/MMDA_(drug)

If using the more common 3,4 numbering for the bridge, in an MDA molecule there'd be no hydrogen at the 3 position and a bond would have to be freed up by removing a double bond from the benzene ring.


----------



## MurphyClox

Dread makes my day


----------



## fryingsquirrel

Turing Machine said:


> It depends on what you mean. The next carbon over from the para position can be numbered either as the 5 position or the 3 position. If you consider the methylenedioxy bridge to be at the 4,5 position it is a Pihkal comound MMDA and it is illegal in both the US and the UK. Also, 3-meo-pcp is not clearly legal in the US it could fall under the analog act. Prosecution is likely if sold for human consumption.
> 
> http://en.wikipedia.org/wiki/MMDA_(drug)
> 
> If using the more common 3,4 numbering for the bridge, in an MDA molecule there'd be no hydrogen at the 3 position and a bond would have to be freed up by removing a double bond from the benzene ring.


Hope you don't object if I translate for the OP-Uhm, no.


----------



## hugo24

To save the thread, N-Methyl-MMDA would be an interesting compound to explore, not sure how much diminished activity it would have compared to other N-Methylphens 5-HT2 agonists. I think only with MMDA-2 or MMDA-3 the respective N-Methyl compounds have been tasted.


----------



## seep

I'm guessing if you take a graduated cylinder and pour in some chloroform, then on top of the chloroform some water, then on top of the water some ether, you'd have a nice 3-phase suspension.  Now then pour a little safrole gently onto the suspension and slowly raise the ambient temperature.  The ether would gradually evaporate until the specific gravity of the ether-safrole layer rises to 1, at which point you'd have turbulence as the safrole deposits through the water and into the chloroform.

This would be slightly more dramatic if the water is saturated with something that keeps the ether and the chloroform from emulsifying with the water.

I'm gonna get a bottle of safrole from a botanica so I can do this experiment.


----------



## (zonk)

From what I've seen methylating amphetamines only works if there is nothing at the 2,5 or 6 positions. Anything at those position turns it into a straight agonist rather than releaser and methylating it would only greatly fuckup/diminish/abolish activity


----------



## dread

(zonk) said:


> From what I've seen methylating amphetamines only works if there is nothing at the 2,5 or 6 positions. Anything at those position turns it into a straight agonist rather than releaser and methylating it would only greatly fuckup/diminish/abolish activity



Uh... wrong, but nice try.


----------



## nuke

6 position is the same as the two position with no substituents.... likewise, the 5 position because the 3 position.  The mono- meta and orthro substituted amphetamines are very active as stimulants.


----------



## melange

can someone tell me if they have heard of evidence of dextromethorphan causing dilated cardiomyopathy


----------



## MurphyClox

melange said:


> can someone tell me if they have heard of evidence of dextromethorphan causing dilated cardiomyopathy


I'm currently not aware of such a connection. What makes you think there is one?


----------



## melange

MurphyClox said:


> I'm currently not aware of such a connection. What makes you think there is one?



I don't know, it's probably nothing.

I am one of those few obscure people that have a real positive affinity to dextromethorphan, and I do it a lot.(please no one judge, or say "do a real drug" because believe me I have done a bunch, real and analogue)

I don't know it is probably in my top 5 of drugs I have ever tried. I get extremely serotonergic effects from it, loved up, empathetic and all that jazz. I have never really had negative effects from it.(until now possibly)

During my increasing use starting about a year ago, I noticed my heart rate and blood pressure would get extremely high on it. It has always stimulated me, but never sympathetic nervous system effects like this. Also I have been getting dysrhythmias when I am not on it. It is only a few skipped beats at a time, but it has been increasing over time since it has started last year. Now it does it once every other day, maybe every day. I admit I am a hypochondriac at times, but I know stimulants can cause this type of cardiomyopathy. I have had numerous ekg's, even on the stuff, and all docs say my heart is normal. I take pretty good care of my body, doing a lot of cardio weekly and eating right. I don't know this is just kind of scaring me, and naturally someone would just say "quit." I am just looking for some kind of answer.


----------



## LivingOnValium

Why does Water/H2O + DCM/Dichloromethane + Methanol/MEOH form a single phase solution? whereas water + DCM is two layers and Methanol + DCM is two layers also.


----------



## MurphyClox

1. DCM and MeOH are miscible.

2. In the ternary mix DCM/MeOH/water, the MeOH serves as solution mediator, being of intermediate polarity, between water and DCM. I would think that the water sticks in such a solution mainly to methanol's OH-group. Therefore, the methanol-content decides how much water you can dissolve in a DCM/MeOH-mix.


Peace! - _Murphy_


----------



## LivingOnValium

^thanks murph!


----------



## dread

I just tried gabapentin the other day, and I experienced extensive visuals both eyes open and closed. I'm curious now, what mechanism could gabapentin have to cause this? My understanding is that it's mechanism of action is similar to that of pregabalin, but I never experienced anything similar on pregabalin.


----------



## MurphyClox

That is _HIGHLY_ unusual for gabapentin ... no real help, I know, but I'd be very suspicious if there couldn't be other reasons for your experience.

- _Murphy_


----------



## pharmakos

i haven't tried gabapentin, but doses of pregabalin around 1g produce pretty nifty open eye visuals for me.  its hard to describe what they were like.  i mostly saw them on blank, white surfaces.  it sort of reminded me of the whispy, smokey visuals that some serotonergics produce on white surfaces, but it was still pretty different.


----------



## melange

I have peripheral neuropathy

I use to take gabapentin 900 mg - 3 times a day

I use to abuse it

I would take 3 grams at a time

the shit would speed me up like meth minus euphoria 

my point for this drug-addled story is that I too have had atypical effects from gabapentin


----------



## melange

listen

---------------


wouldn't be cool to use our liver

like our metabolites - to make new drugs - we eat something, let the liver do the work- - make the metabolite yada yada extraction profit?   I'm high, I am sorry


----------



## dread

MurphyClox said:


> That is _HIGHLY_ unusual for gabapentin ... no real help, I know, but I'd be very suspicious if there couldn't be other reasons for your experience.
> 
> - _Murphy_



Well I don't see what else could have caused it. I didn't do any other drugs that day. 

Something about those visual effects was weird. Like I would try to watch a movie on tv, it turned out to be impossible - it felt like my brain didn't process the visual information fast enough, every time the camera angle changed in the movie it took a second or two for me to grasp the visual information and see the picture again...

I also experienced some nystagmus. Eyes closed, I saw colourful patterns, not fractal-lice but more chaotic.

Granted, the dosage I took was quite large (around 7 grams).


----------



## nuke

dread said:


> I just tried gabapentin the other day, and I experienced extensive visuals both eyes open and closed. I'm curious now, what mechanism could gabapentin have to cause this? My understanding is that it's mechanism of action is similar to that of pregabalin, but I never experienced anything similar on pregabalin.



Gabapentin causes pretty wacky visuals in me, not like those of psychedelics but usually more simple and blurrier.  When you combine with opiates things get really weird, once I had about 2 grams of gabapentin with 15mg hydrocodone and went to watch some fireworks, and I couldn't tell the normal sky from the fireworks about half the time!  Not to mention everything was extremely blurry.  Really weird stuff.


----------



## Vader

Could gabapentin produce visuals in a manner similar to the Z-drugs? Are the mechanisms of action similar?


----------



## MurphyClox

...what is the safety margin of gabapentin?


----------



## dread

nuke said:


> Gabapentin causes pretty wacky visuals in me, not like those of psychedelics but usually more simple and blurrier.  When you combine with opiates things get really weird, once I had about 2 grams of gabapentin with 15mg hydrocodone and went to watch some fireworks, and I couldn't tell the normal sky from the fireworks about half the time!  Not to mention everything was extremely blurry.  Really weird stuff.



Well that explains somewhat, I have a buprenorphine medication so it might have interacted with the gabapentin somehow?

Yeah the visuals I got were nothing like those you get on psychedelics - in a way they're completely opposite... on psychedelics, the visuals feel like the brain is over-processing all the visual input, while on gabapentin it feels like the brain doesn't process the visual input fast enough...



> ...what is the safety margin of gabapentin?



I understand it to be pretty wide... even a dosage of several grams doesn't seem to cause any notable adverse effects (except for a terrible dryness of mouth.)


----------



## fryingsquirrel

MurphyClox said:


> ...what is the safety margin of gabapentin?


Apparently quite wide. I've seen my wife take 50 grams (not a typo) of the stuff on more than one occasion, without any obvious problems.

I recently noticed closed eye visuals (quite enjoyable) for the first time, I'm sure they've been there all along had I looked for them. This was at I think 3600 mgs.


----------



## MurphyClox

Thanks for the responses. Make me curious...


----------



## Memeito

What does nifty means?


----------



## dread

http://en.wiktionary.org/wiki/nifty


----------



## fryingsquirrel

Memeito said:


> What does nifty means?


It's one of those odd terms organic chemists use. And my grandma.8)


----------



## nuke

fryingsquirrel said:


> Apparently quite wide. I've seen my wife take 50 grams (not a typo) of the stuff on more than one occasion, without any obvious problems.
> 
> I recently noticed closed eye visuals (quite enjoyable) for the first time, I'm sure they've been there all along had I looked for them. This was at I think 3600 mgs.



These are noteworthy too actually, especially with opiates.  Normally I get dreamy sorts of states with opiates, but when I mixed hydrocodone with gabapentin on another occasion, when I closed my eyes I would have really vivid full-blown fantasies, like I imagined I was in another room and was wandering around the room looking at different objects and for a while thought I was actually in it

The safety margin is high, but you have to be careful about it.  After some really large doses I got really bad tremors and I would be afraid that if you used it regularly for a while and suddenly stopped it might cause seizures, like benzodiazepines.  But that I mixed it with relatively high doses of hydrocodone (for me, 20mg is a strong dose), seemed to indicate it was all too good at respiratory suppression.  I think my highest dose was 6 grams, but that was before I knew about the weird absorption.  Now 1200mg spaced over a longer timeline has the exact same effect.


----------



## kken

why do amphetamines sedate me in low doses? does this happen to every person or only to people who are diagnosed with attention disorders

would the mechanism be related to serotonin. eg MDAI really sedates me


----------



## kken

melange said:


> I have peripheral neuropathy
> 
> I use to take gabapentin 900 mg - 3 times a day
> 
> I use to abuse it
> 
> I would take 3 grams at a time
> 
> the shit would speed me up like meth minus euphoria
> 
> my point for this drug-addled story is that I too have had atypical effects from gabapentin



are you surer this is atypical effect? me and everyone ive talked with who abused pregabalin or gabapentin and large doses seem to be stimulating in a sense indeed (you can still sleep but you dont feel the need to)

for me to reach this i have to take large doses (1g pregabalin which is like what, 15g of gabapenting )



Yerg said:


> Could gabapentin produce visuals in a manner similar to the Z-drugs? Are the mechanisms of action similar?



No


----------



## THCDunc

*4-MeMABP*

Seeing as the thread on this topic has been closed I thought I would ask my question here. 

This morning I recieved a sample of this compound, I've done an allergy test with 1-2mg and all seems good so far, I haven't had a reaction and I haven't dropped dead. 

The thing i'm worried about is toxicity, I know it will be toxic as para substituted cathinones always are but just how toxic are we talking? I know no one can give me a definative answer I just want some reasurance that i'm not going to drop dead.


----------



## fryingsquirrel

kken said:


> are you surer this is atypical effect? me and everyone ive talked with who abused pregabalin or gabapentin and large doses seem to be stimulating in a sense indeed (you can still sleep but you dont feel the need to)


Agreed, I don't believe those affects atypical at all.


----------



## melange

well I don't know, the stimulation I get is really extreme. Like bouncing off the walls, to the point of mania. I guess I am not alone then.


----------



## brahma_bull

Phenibut is supposed to induce relaxation and sleep, well it makes me hyper...energized with no intention of relaxing....weird.


----------



## /navarone/

*How dumb is this LSD analogue?*

Sorry if this might sound a bit dumb. This is going to be a very short thread I guess but I didn't know where to ask.
After some research on 5-HT2a receptors and overlapping various psychedelics like Bromodragonfly, 5-MeO-DMT, DOB and LSD, a certain scheme seems to emerge (at least in my head).
Also on chemspider and pubchem I also saw a couple LSD analogues never discussed here. Theese where 5-OH-LSD, 5-MeO-LSD (and also the dimethylaziridine version of LA-ss-Az BTW but let's put that aside). Wiki also states that the trifluoromethyl version of 2CB-FLY is much more potent than the former.
Well I know that psychoactive chemestry isn't really like playing Lego but i wanned to hear from you your expectations on the following substance and how it could be bettered.






I pur an R since I was really undecided what to put on the 6-N considering that ETH-LAD is more potent but has a greater tendency to spontaneously decay even at 0°C. PRO-LAD is more pontet but shorter acting. AL-LAD also seems to be nothing that special and I haven't found any concrete info on CYP-LAD and FLUORETH-LAD (though this last one seems to fascinate some BLs)

I apologize in advance if this might be a naive suggestion.
(Murphy please be gentle this time)


----------



## dread

Fluoreth-LAD seems like one of shulgin's worse ideas to me... wouldn't that produce fluoroacetate as a metabolite?

As for your chemwank... I don't think you can extrapolate from phen/trypt SAR to lysergamides. They bind differently I think...


----------



## atara

Well, I don't think that the dimethylazetidide really adds much potency, and at the same time it makes it way harder to synthesize and it probably (this is just a guess) decreases action at a number of other non-5ht2a receptors that may have partially been responsible for LSD's magic. 

I've wondered for a while if 7-substitution of tryptamines would add something interesting, though, ever since I heard about this stuff.



dread said:


> Fluoreth-LAD seems like one of shulgin's worse ideas to me... wouldn't that produce fluoroacetate as a metabolite?



If it's active in the 100 ug range, it'll produce a scary 5 ug of fluoroacetate. I think that's not terribly concerning. When your doses are as small as they are with the lysergamides, you tend to not worry as much about toxic metabolites.


----------



## /navarone/

Somehow it seems that both psych-phens and trypts share some SAR when speaking of 5-HT2a.

To confirm this a subtance like (4S) N,N-dimethyl-1,3,4,5-tetrahydrobenzoindol-4-amine should be tested for psychedelic activity.

Though this does not explain why primary amine tryptamines are almost non active while primary amine psychedelic phenylethylamines are...


----------



## atara

/navarone/ said:


> Though this does not explain why primary amine tryptamines are almost non active while primary amine psychedelic phenylethylamines are...



Tryptamine is active, for about seven minutes:

http://www.erowid.org/library/books_online/tihkal/tihkal53.shtml

I'd assume they're destroyed really quickly by MAO, since AMT is perfectly active and it's a primary amine tryptamine.


----------



## golden1

atara said:


> Tryptamine is active, for about seven minutes:
> 
> http://www.erowid.org/library/books_online/tihkal/tihkal53.shtml
> 
> I'd assume they're destroyed really quickly by MAO, since AMT is perfectly active and it's a primary amine tryptamine.



I've been wondering what effects(if any) tryptamine produced, thanks. I was certainly thinking it would be active since it is very similar to dmt and serotonin.

He also says that tryptophan is converted to tryptamine while from what I can see the pathway is tryptophan > 5-htp > serotonin > normelatonin > melatonin. Is it converted to tryptamine, maybe to a lesser amount or did he have the wrong information?

I've tried l-tryptophan sublingually in the past and I had intermittent visuals(moving things had an acceleration and kept moving even after they had stopped, trails, after images, things looked bright and novel), however I had done DPT the night before so I'm not so sure I can attribute it to tryptophan.


----------



## atara

http://en.wikipedia.org/wiki/File:5htsynt_2.png


----------



## Phener

hmm did shulgin ever try 4-ho-tryptamine, just thought if it worked IV that could actually be REALLY experimental to have a super FAST acting psycadelic.


----------



## mgrady3

Assuming that the byproducts really aren't produced in big enough quantities, then an Ethyl on the 6-N may be interesting if it was stable. Personally I'm not too thrilled about continuously tacking on subtle changes,  ie. 2C-I,B,T,T7,  oh-lsd, meo-variants, etc. But it may be worth pursuing


----------



## Astavats

/navarone/ said:


> [Your molecule]



D.E. Nichols has mentioned he was planning on making a few LSD metabolites to test the activity of with his Purdue research team. He specifically mentioned one with a hydroxyl on the benzene (13-HO-LSD, if I recall correctly) giving his personal suspicion of why it would be active, lab rat changes in response to light and sound over time, etc. that jazz in detail. This was supposed to be published July/June 2010 but I've yet to see/hear anything of it yet. Either way I think it makes sense (re: 13-OH-LSD) both logically and when you look at the binding pocket.

As for your specific molecule I personally don't think it will fair so well at 5-HT2A. My reasons are; 
1) The furan ring's oxygen is on the the incorrect side, as far as I see it working - sure, in a phenethylamine it would be correct, however LSD is tilted quite different than PEAs when docking. 
2) It makes more sense (for me) to start with OH, MeO, Me, Eth working way up to a trifluoromethyl group instead of copy-pasting from 2C-TFM. 
3) Furan _might_ destroy pi-pi interaction in general, specifically with the benzene on LSD with phenylalanine (Phe340), if not most likely hinder it. Any chemists want to correct me?

That's my thoughts, can't promise it is without fault however.


----------



## /navarone/

^ I see, however i don't quite get what u said about the furan oxygen, The oxygen is exactly at the same carbon than 5-Meo-DMT, and for what I've seen so far LSD seems to follow all th tryptamine rules when speaking of pychedelic activity. I don't see how the oxygen at the other side would allow hydrogen bonding. (BTW has a furan or dihydrofuran analogue of 5-MeO-DXT ever been tested?)
Also about the furan interacting with the pi-pi activity, I knew that BOD was quite active as well even if it has a beta methoxy wich compensates for the negative charge activity of the LSD 9-10 doublebond. Do these 2 groups compete for the same hydrogen bonding when docking?

I obviously don't know that much about 5-HT2a docking. A grat deal of what i know so far comes from an amazing thread by F&B about 5-HT2a SAR which I'll link below.

http://www.bluelight.ru/vb/showthread.php?t=167978


----------



## fryingsquirrel

nuke said:


> After some really large doses I got really bad tremors and I would be afraid that if you used it regularly for a while and suddenly stopped it might cause seizures, like benzodiazepines.


My wife has taken gabapentin at grams daily, with whole bottle taken in a day often. Long term, perhaps ten years, though  of course doses did not start at that level. Recently she was in jail for about a week without meds and when she was released I obseved what gabapentin WD's at what I assume are about as bad as they likely get. And of course the underlying bi-bolar which she is prescibed these she has other scripts for fibromyalgia (sp?) among others but the BP is the true reason. While she was a mental wreck (jails probably didn't help) I saw no physical issues. No tremors and certainly no seizures. However she had feeling of suicide. The with WD's seem to be purely mental but very bad.One person is not a case study of course.


----------



## Astavats

/navarone/ said:


> ^ I see, however i don't quite get what u said about the furan oxygen, The oxygen is exactly at the same carbon than 5-Meo-DMT, and for what I've seen so far LSD seems to follow all th tryptamine rules when speaking of pychedelic activity.



The methoxy can more freely accommodate the oxygen unlike the furan ring however. As I said, it's from my understanding and is given with no guarantee of being 100% correct. From the docking layouts it seems like it wouldn't work on LSD, but who knows.

You should read Towards a biophysical understanding of hallucinogen action., some other Nichols' work and RA Glennon (if you haven't) if you want to better understand the binding pocket of 5-HT2A. There are other works by other researchers but I'm not on _my_ computer currently. You'd be able to answer your own question about the drawn compound after, most likely.


----------



## chrisl21

*Production*

Ok, so i can get 1kg of coke paste.
How do i cut it? I was thinking of adding 2 - 5% beta blockers. This can prevent your heart from going haywire in case the user takes to much. Might even extend the level where od happens!
Whats your thougts?


----------



## Swerlz

no and no...


----------



## LivingOnValium

chrisl21 said:


> Whats your thougts?



You're fucked mate. Incriminating yourself for getting a kg of coke isn't the smartest thing do. That's what first comes into my mind.. 8)


----------



## Brian.Badonde

Hi

Its a good theory, but combining cocaine with beta blockers is DANGEROUS as the body will have unopposed alpha channel activity.

Please do not do it as you could seriously endanger someones life!

For more info / detailed explanation: http://www.themagellangrp.com/coursepdf/CocaineOverdose.pdf

Thank you.

Brian Badonde.


----------



## homeydontplaythat

*pregabalin IV vs PO*

i noticed that pregabalin (lyrica) is not as effective IV as it is orally.  anyone have any reasoning for this?


----------



## fryingsquirrel

No, but my wife says snorted gabapentin (neurontin) is not as effective as oral.

She snorted 2400 mgs.

She is fucking retarded.


----------



## Swerlz

I believe it has something to do with having to go through first-pass metabolization (through the liver)


----------



## fryingsquirrel

Swerlz said:


> I believe it has something to do with having to go through first-pass metabolization (through the liver)


Yes, I believe that correct.

Sorry, at a point in my life where calling the wife a retard is a higher prority than passing on information. I have issues.


----------



## chrisl21

Mr valium man, read again. I said i can, and not i have or will. 
damn about the b blockers. Having been on the brink of od my self i thought they wil only prevent that last line from making your heart feel like it is exploding.


----------



## naginnudej

Can anyone help me identify this?

1-(3,4-Methylenedioxyphenyl)-2-methyl-2-pyrrolidinyl-1-propanone


----------



## MurphyClox

naginnudej said:


> Can anyone help me identify this?
> 
> 1-(3,4-Methylenedioxyphenyl)-2-methyl-2-pyrrolidinyl-1-propanone







Are you sure that you got the name right?

- _Murphy_


----------



## naginnudej

I was thinking the same thing but it showed up in this this test.

A erowid crew member asked me to look into it but I can't seem to find anything. It's either very very new or a misprint. My gut says the latter; perhaps it's this? 

Thanks for the help Murph


----------



## vortex30

chrisl21 said:


> Mr valium man, read again. I said i can, and not i have or will.
> damn about the b blockers. Having been on the brink of od my self i thought they wil only prevent that last line from making your heart feel like it is exploding.



That's exactly the problem man. It won't FEEL like it is about to explode but in reality it still IS under excessive pressure and one should be aware of these sensations so they stop what is causing them, they shouldn't be unaware of them. Ignorance is bliss until it kills you.


----------



## MurphyClox

naginnudej said:


> I was thinking the same thing but it showed up in this this test.
> 
> A erowid crew member asked me to look into it but I can't seem to find anything. It's either very very new or a misprint. My gut says the latter; perhaps it's this?


I must emphasize that the name "1-(3,4-Methylenedioxyphenyl)-2-methyl-2-pyrrolidinyl-1-propanone" is not 100% unambiguous. The following structure could also fit (although it is highly unlikely):





My vote still goes to the molecule shown in my last post.


Peace! - _Murphy_


----------



## dread

> My vote still goes to the molecule shown in my last post.



Me too. The first one would be like a pyropropiophenone analogue of phentermine. I've actually wondered if that chemical would be active, and seems it is if it's showing up on some powder.

btw, anyone notice that powder also contains ethylamphetamine? neat.


----------



## FloridaHighs

lol ethylamphetamine = first  effective weight loss supplement


----------



## homeydontplaythat

no, there is no metabolization of this drug.


----------



## irobeth

iirc studies show that almost 100% of the drug is excreted (via renal pathways) unchanged.

A quick read shows that it exerts action on glutamic acid decarboxylase so maybe it passing through the liver anyway is required for its action? I don't know anything about enzymes really.


----------



## kokomo

it aint effective at any ROA for me
(is this a serious thread btw?)


----------



## Jamshyd

This is, once again, OD or BDD material.

And the reason it is effective is because pregabalin, like gabapentin, is taken up actively (like amino acids), not absorbed, in the gut. This means there is a limit to how much actually gets to your blood. When you IV, you bypass that barrier. That said, IVing capsules is a horrendous idea and can lead to things like infected abscesses and gangrene. If you think it is worth it, go nuts.


----------



## homeydontplaythat

i still dont understand why IV does not work.  bypassing first pass metabolization would be good for most drugs.  this drug isnt metabolized at all, so sending it straight across the BBB seenms as if it would more effective than oral use.  the BA is alrady 90% so really it would just be a quicker onset, but it doesnt seem to last at all.  


when you take pregabalin orally it takes 1.5 hrs to Cmax, and that is VERY accurate.  IV, you can feel it within 1 minute but it just dissapears.  there is no plateau at all.  im totally stumped.  ive never used a drug where iv use was not far superior to oral. 

there are some drugs, like tramadol, where the metabolite is the active drug and bypassing metabolization with IV renders it useless.  however, pregab is not metabolized at all.  does this make sense to anyone else or is it just me?


----------



## Hammilton

I'm pretty certain that pregabalin and gabapentin are both actively taken into the brain, not just through the gut.  They're unable to cross the blood brain barrier and instead are taken up by an amino acid transporter (I forget which one- lysine springs to mind for some reason).

IIRC, that is.


----------



## MurphyClox

I agree with Hammilton. Active transport happens from the guts into the blood stream (which can be bypassed by injection) AND from the blood stream into the brain (which can't be bypassed by any means).

- _Murphy_


----------



## homeydontplaythat

_I'm pretty certain that pregabalin and gabapentin are both actively taken into the brain, not just through the gut_
[I
]AND from the blood stream into the brain (which can't be bypassed by any means).[/I]


so how would this exempt IV use of a drug that is not even metabolized?  its not that there are no effects at all, it is just that they effects are greatly diminished.


----------



## melange

I am very interested in stem cells inserted into the hippocampus

anyone with any familiarity feel free to participate/contribute


----------



## DeMiZe-420-

is it possible for the neurotransmitters destroyed in your brain from drug use to be repaired/restored?


----------



## MagickalKat777

DeMiZe-420- said:


> is it possible for the neurotransmitters destroyed in your brain from drug use to be repaired/restored?



They're all repaired eventually... The brain isn't born with a set amount of a given neurotransmitters which are used for the rest of your life. Neurotransmitters are used and expelled and replaced just like blood cells are. The problem is that most people don't give their brain enough time to recover or they don't give their brain the fuel it needs to replace those lost neurotransmitters.

Example: L-Glutamine - GABA
5-HTP or L-tryptophan - Serotonin
L-tyrosince - Norepinephrine


----------



## MurphyClox

... "destroyed"... "repaired" ... come on guys, we are talking about living systems here. The compounds may get _catabolized_ or _anabolized_ or _transformed_ but nothing is 'destroyed' here. Don't get too sloppy with these terms please.

- _Murphy_


----------



## ebola?

I believe that the poster was intending to ask about whether if background intercellular levels of a given neurotransmitter fall, the brain will reattain the prior homeostasis at some point.  Of course, without knowing the specifics of which neurotransmitters are involved and which mechanisms caused this homeostatic shift, no one can say much.

For most recreational drugs, I'd concern myself more with receptor-downregulation, excito-toxicity, and mitochondrial damage due to free-radical formation.

ebola


----------



## Lombergerh

I'm a little confused:
Bufotenine(5-HO-DMT) is the ether of psilocin(4-HO-DMT) ?
5-meo-dmt is the ether of bufotenine?
If it is wrong,  5-meo-dmt is the ether of what substance ?


----------



## MurphyClox

^5-MeO-DMT is the methyl-ether of bufotenine. As you already wrote correctly, the OH in psilocin is in position 4 and won't move. The methyl-ether of psilocin is - _surprise, surprise_ - 4-MeO-DMT.

- _Murphy_


----------



## dread

Bufotenine is a structural isomer of psilocin.


----------



## <pyridinyl_30>

I was just reading a thread over in Psychedelic Drugs about N-BOMe-Mescaline, and it made me wonder:

Are N-(2'-methoxybenzyl)-amphetamine's and N-BOMe-MDA's effects known?

I know that the former is related to benzphetamine.


----------



## Vader

There are multiple reports of freebase DMT being active when snorted. My understanding was that, as it is not water soluble, it would not be absorbed by the mucous membranes, and would end up being swallowed and chopped up by MAO. What am I missing?


----------



## ebola?

There are a couple of exceptions to the non-water soluble, non-insufflatable rule.

ebola


----------



## Vader

Evidently, but could you explain _why_ this is please? I just don't get it.


----------



## mukaki

Hey

I'm just wondering if Kava MAO inhibition is significant enough to cause problems with taking common anti-depressants, in this case Edronax (reboxetine (an NRI)). I've taken kava three times with no ill effect except maybe a little elevated heart rate the first time, but that might have been placebo. Then I read about that an alkaloid functions as a MAOI-B, so now I'm wondering, am I hurting myself or is it just not powerful enough when the alkaloid is not pure and therefore is in small dosages.

Dunno if this is really a simple question, but I don't want to start a new thread if it's completely obvious


----------



## Sturnam

MAO-B selective inhibitors are not nearly as dangerous as MAO-A inhibitors, so it's good that it's MAO-B selective. As far as danger, I would say just listen to your body, and if you think that your heart rate or blood pressure is too high, then stop using.


----------



## mukaki

Thank you


----------



## ebola?

Because MAOA preferentially metabolizes NE and 5HT, selective inhibition of MAOB (which preferentially metabolizes DA) shouldn't theoretically prove very dangerous.  In all likelihood, the inhibition from Kava is weak, but please take care, and listen to your body, and also dose such to avoid crossover into MAOAI (if this is possible).

ebola


----------



## Captain.Heroin

Yerg said:


> Evidently, but could you explain _why_ this is please? I just don't get it.



Other examples of drugs you can snort, but are not water soluble, would be benzodiazepines such as triazolam.  



homeydontplaythat said:


> im totally stumped.  ive never used a drug where iv use was not far superior to oral.



Flurazepam seems to work better orally as well.


----------



## dread

> Other examples of drugs you can snort, but are not water soluble, would be benzodiazepines such as triazolam.



Triazolam is water soluble at least as the tartrate salt (in which form it is most often supplied.)
Same with midazolam. IIRC this is due to each having an azole ring (imidazole or triazole) which is basic enough to form a salt.

The vast majority of benzodiazepines however do not have this property and are inactive if snorted.


----------



## Antavio09

*Anybody have anything to add to my op prep?*

It requires the pill to be ground into a fine powder, preferably with a metal file. THE PILL CANNOT GET WET WHILE GRINDING. I am basing this off 40mg op that I  have been experimenting with. 

1. grind pill to powder
2.get container place 4cc's of h2o2(hydrogen peroxide) and 4cc's of white vinegar together, then mix.
3.place op powder into mixture.
4.swirl container containing solution to mix up.
5. leave container for hour it will completely break down. no goo like with the coke method.
6.Once broken down, you are not finish this mixture is not yet ingest-able. the hydrogen peroxide has to be broken down into its baser elements.
7.Heat the solution to 120f-150f  or very low on a stove top.
8.As you do this the solution will slowly evaporate which is ideal as to not to destroy the oxycodone. The low heat breaks the bonds of the peroxide by turning it into its two harmless components water and hydrogen.
9.As you heat all of the solution away You will be left with your final product stuck to the bottom of the solution container.


----------



## seep

Antavio09 said:


> It requires the pill to be ground into a fine powder, preferably with a metal file. THE PILL CANNOT GET WET WHILE GRINDING. I am basing this off 40mg op that I  have been experimenting with.
> 
> 1. grind pill to powder
> 2.get container place 4cc's of h2o2(hydrogen peroxide) and 4cc's of white vinegar together, then mix.
> 3.place op powder into mixture.
> 4.swirl container containing solution to mix up.
> 5. leave container for hour it will completely break down. no goo like with the coke method.
> 6.Once broken down, you are not finish this mixture is not yet ingest-able. the hydrogen peroxide has to be broken down into its baser elements.
> 7.Heat the solution to 120f-150f  or very low on a stove top.
> 8.As you do this the solution will slowly evaporate which is ideal as to not to destroy the oxycodone. The low heat breaks the bonds of the peroxide by turning it into its two harmless components water and hydrogen.
> 9.As you heat all of the solution away You will be left with your final product stuck to the bottom of the solution container.



interested in this.  Can you specify whether you used 3% or 6% peroxide?  Also, if it interests you, you may want to try to measure the melting point of your extract.  You don't need a melting point apparatus you can McGuyver a Thiele tube (watch The French Connection from 52:00 to 54:00 they show it very clearly).


----------



## mukaki

ebola? said:


> Because MAOA preferentially metabolizes NE and 5HT, selective inhibition of MAOB (which preferentially metabolizes DA) shouldn't theoretically prove very dangerous.  In all likelihood, the inhibition from Kava is weak, but please take care, and listen to your body, and also dose such to avoid crossover into MAOAI (if this is possible).
> 
> ebola



So it wouldn't theoretically be dangerous because I take no other drugs that mess with dopamine, whereas if I was to take a MAOBI with for example cocaine it would end in psychosis?

Thank you for your response btw.


----------



## Antavio09

seep said:


> interested in this.  Can you specify whether you used 3% or 6% peroxide?  Also, if it interests you, you may want to try to measure the melting point of your extract.  You don't need a melting point apparatus you can McGuyver a Thiele tube (watch The French Connection from 52:00 to 54:00 they show it very clearly).



just the 3% h202, I'm using everyday over the counter products. this is just my first endeavors into fucking with the new formulation. I have not been very precise because I'm still tweaking the process. My next step is to introduce grain ethanol into the mix at a concentration of 20% of the total concoction. I think with the ethanol it will provide a more even evaporation to the whole process and possibly curb the polyox. Everybody on here is talking about microwaving it and shit like that, they are going about it the wrong way. you  have to think in terms of what does the stomach and small intestine do. appreciate the feedback


----------



## ebola?

> So it wouldn't theoretically be dangerous because I take no other drugs that mess with dopamine, whereas if I was to take a MAOBI with for example cocaine it would end in psychosis?
> 
> Thank you for your response btw.



Theoretically, the interaction should be minimal (as the two MAOs overlap minorly in target), but I'd take caution; there's a lot left to be researched about the relevant science.  

Inhibition of MAOB combined with dopaminergics is very risky.

ebola


----------



## mukaki

Okay, then I think I got it. Don't worry I'm not planning of combining with a dopaminergic or anything like that. I'll take care and experiment slowly


----------



## Captain.Heroin

dread said:


> Triazolam is water soluble at least as the tartrate salt





> Triazolam (Halcion) - 0.00453 mg/mL



Extremely poor water solublility if you ask me.


----------



## MurphyClox

...he meant the *tartrate* salt! The free base is - of course - practically insoluble in water. - _Murphy_


----------



## melange

^lol


----------



## Captain.Heroin

MurphyClox said:


> ...he meant the *tartrate* salt! The free base is - of course - practically insoluble in water. - _Murphy_



Can I get a source on what triazolam tartrate's water solubility, then?


----------



## dread

Oops... I meant maleate, not tartrate.


(not that it makes much difference in this case. )


----------



## MurphyClox

...looks like Mr. Dread fooled us. I can't find any info about neither triazolam tartrate nor its maleate. Both are certainly - _theoretically_ - soluble in aqueous solutions, but it looks they were never published anywhere.  Are you sure you didn't mean midazolam instead?

Gimme a CAS or something in case I'm wrong and I'll look again.


Peace! - _Murphy_


----------



## dread

Well I can't speak with 100% certainty since it's been years since I've had any halcions, and my memory might fail me. But I seem to distinctly remember the package of the pills speaking of a triazolam salt. 

Of midazolam, I _am_ sure: midazolam is sold as the maleate monohydrate. 

Of triazolam I can only offer anecdotal evidence: the pills I had were readily water-soluble & effective with IV administration.. and since freebase triazolam is poorly soluble in water, I see no reason to assume that they were anything other than a salt...


----------



## melange

the future is here


all this talk about marijuana legalization(believe me, i'd love it to happen)

I can goto my corner store and buy 3 grams of potent cannabinoid analogues for 14 dollars


----------



## melange

dextromethorphan freebase

I wonder if the melting point is low enough where this would be fun


----------



## Vader

Would you not have to smoke an awful lot of it?


----------



## melange

true


----------



## Thorns Have Roses

Plus, I don't know that having so much dextromethorphan in your system would be desirable. Isn't the general goal to have as much converted into dextrorphan as possible, and as quickly as possible, hence the exclusive use P.O. route to take advantage of first pass metabolism?


----------



## Slapdragonx

It would appear DXM freebase's boiling point is too high to easily vapourize and if you do go through with it, it is very hard on the longs.


----------



## melange

I always get these mixed up

did I mean boiling or melting point?

are they the same

---edit- I searched and it seems they are different 



noob moment over


----------



## MurphyClox

LOL!

Melting = transition from the solid to liquid state
...Freezing = the same transition but in the opposite direction
Boiling = transition from the liquid to gaseous state
...Condensing = the same transition but in the opposite direction
Sublimation = transition from the solid to the gaseous state without passing through the liquid one.

_Basic lesson over._


Now when it comes to smoking it seems that people are often underestimating this way of application when looking at the respective boiling points. We recently had the discussion if methylphenidate-freebase could be smoked. I tried to demonstrate that this should indeed be possible by comparing the physical data with cocaine's, of which we know with _certainty_ that it can be smoked. Follow the above link for the full discussion, but in short here again the values:

Cocaine-freebase:
m.p. = 98 °C
b.p. = 187-188 °C @ 0.1 Torr​
Methylphenidate-freebase:
m.p. = 74-75 °C
b.p. = 135-137 °C @ 0.6 mmHg​
Dextromethorphan-freebase:
I found several conflicting melting points:
80 °C (_J Pharm Sci_ *1962*, 51, p.931)
109-113 °C (Clarke's Isolation and Identification of Drugs)
109.5-112.5 °C (Hager's Handbuch der Drogen und Arzneistoffe and USP 33-NF 28 )
126 °C (_Int J Chem Kinetic_ *2008*, 40(9), p.559)
...but the last one seems to be incorrectly attributed and rather belongs to the hydrobromide salt (says "Clarke's" again). 109-113 °C looks like the genuine value.
Dextromethorphan decomposes upon attempting to distill it, so the final answer is NO, it can't be smoked.​

Peace! - _Murphy_


----------



## melange

murphy you are so awesome and thorough 



THANKS


----------



## pharmakos

what about an inhaler-like style of administration?


----------



## MurphyClox

_Maybe_ possible, but how much do you want to inhale?

And *please*: Don't even think about inhaling the ready cough-suppressant solutions availble in pharmacies. They contain all other kind of stuff, like (sometimes) paracetamol, sugars, colorants, ...


- _Murphy_


----------



## Slapdragonx

The active dose is likely to be too much to easily apply to inhalation.


----------



## Vader

> Melting = transition from the solid to liquid state
> ...Freezing = the same transition but in the opposite direction
> Boiling = transition from the liquid to gaseous state
> ...Condensing = the same transition but in the opposite direction
> Sublimation = transition from the solid to the gaseous state without passing through the liquid one.


Is there a term for the transition from gaseous to solid state, that is, "backwards sublimation"?


----------



## Solipsis

Yerg said:


> Is there a term for the transition from gaseous to solid state, that is, "backwards sublimation"?



Deposition

as in "assume deposition!"


----------



## seep

dread said:


> Well I can't speak with 100% certainty since it's been years since I've had any halcions, and my memory might fail me. But I seem to distinctly remember the package of the pills speaking of a triazolam salt.



I haven't seen triazolam at all for I don't know how many years, but the triazole and imidazole benzos are easier to protonate because they lack the amide moiety*.  I take it this is easier with the imidazoles than with the triazoles.

The benzos with an amide group at positions 1 and 2 (which is most of them I think) tend not to appear on the market as salt formulations because they *1)* irreversibly hydrolyze when reacted with a strong acid and *2)* are too weakly basic to react with weaker acids.  

See also benzos with a proper amine group (like flurazepam or chlordiazepoxide). The amine group is basic enough to form a stable salt when reacted with a strong acid.  

I suspect that for any traditional (amide moiety) benzos, if the acid isn't dilute enough then the irreversible hydrolyses will take place so I think the DIY people should tread lightly. 

There's also the oddball case of chlorazepate, which has a carboxylic acid group and so is often the anion of a metal salt.

*I hate this word


----------



## any major dude

*magnesium & bruxism*

I was curious about what amount of magnesium & when one should take it to avoid jaw clenching with stimulant/empathogen type substances (MDMA, M1, etc)

I've read that in treatment of non-drug induced bruxism 100mg a day was recommended, but this is obviously a bit different.  Also, the magnesium tablets I have are 500mg, I was thinking one of these a couple hours beforehand should suffice, but wanted to check here as well.

On a more semantic note, is there a difference between bruxia & bruxism?  I keep seeing these used seemingly interchangeably, but wasn't 100% sure.


----------



## Solipsis

any major dude said:


> I was curious about what amount of magnesium & when one should take it to avoid jaw clenching with stimulant/empathogen type substances (MDMA, M1, etc)
> 
> I've read that in treatment of non-drug induced bruxism 100mg a day was recommended, but this is obviously a bit different.  Also, the magnesium tablets I have are 500mg, I was thinking one of these a couple hours beforehand should suffice, but wanted to check here as well.
> 
> On a more semantic note, is there a difference between bruxia & bruxism?  I keep seeing these used seemingly interchangeably, but wasn't 100% sure.



IME 500 mg is fine, but it's not right to use magnesium that also has a certain amount of calcium with it because it might defeat the purpose (not entirely sure though). I also heard you don't want magnesium oxide but don't know what it is you do want.

Bruxia appears to be the latin proper medical name and bruxism the somewhat colloquial effluent English trivial name. But I am not an M.D.

By the way I found 500 mg adequate, those huge tabs that dissolve in water with a lot of bubbles. Seemed like a good fast method of delivery and seemed to work.


----------



## pharmakos

MurphyClox said:


> _Maybe_ possible, but how much do you want to inhale?
> 
> And *please*: Don't even think about inhaling the ready cough-suppressant solutions availble in pharmacies. They contain all other kind of stuff, like (sometimes) paracetamol, sugars, colorants, ...
> 
> 
> - _Murphy_



hah.  well, if i were to go through the trouble of creating an inhaler for dosing of recreational drugs, DXM probably wouldn't be my choice for the inhaler.  i might try it once though, if i had 98+% pure DXM though.

well, for whatever you'd want to dose, i bet you could modify a nebulizer to deliver your DOC to your lungs.


----------



## Turing Machine

*Antiretroviral abuse in South Africa?*

Could someone please explain this to me? I know much of what happens in South African ghettos is difficult to understand, let alone explain. Is this just ramblings of some poor delusional reporter, and a phony charity trying to make money off of some nonexistent drug epidemic or is there something I'm missing?

http://blogs.aljazeera.net/africa/2010/10/22/whoonga-cruelest-high


----------



## Thorns Have Roses

I believe the abused retroviral drugs are NMDA receptor antagonists, but some of that article sounded kind of iffy, I mean rat poison? Come on guys, that's pretty far-fetched.


----------



## atara

The adamantamines, which are NMDA-antagonizing antivirals, are antiinfluenza, not antiretroviral. Different sort of thing.

Antiretroviral abuse is a very surprising thing to see! Though I'd place a similar level of credibility on it as jenkem.


----------



## Thorns Have Roses

atara said:


> The adamantamines, which are NMDA-antagonizing antivirals, are antiinfluenza, not antiretroviral. Different sort of thing.
> 
> Antiretroviral abuse is a very surprising thing to see! Though I'd place a similar level of credibility on it as jenkem.



Whoops, my mistake.


----------



## Turing Machine

Here's an article that seems a bit less sensational in that it doesn't mention rat poison and detergent. The vague description does seem like NMDA antagonism could be a possibility, although looking at the drug it does look like it could function similar to benzodiazepines and even causes false positives for benzodiazepines in urine immunoassay.

http://abcnews.go.com/Health/MindMoodNews/story?id=7227982&page=1

http://journals.lww.com/aidsonline/...esults_of_screening_for_illicit_drugs.30.aspx


----------



## melange

this sounds similar to the tamiflu story I  read about a while ago


----------



## atara

http://news.bbc.co.uk/2/hi/africa/7768059.stm


----------



## StaySedated

i've heard of it, the antiretroviral mentioned has dissociative effects(likely a NMDA antagonist). really this is kinda old news as i heard about this a while back.


----------



## seusemgoose

I know this doesn't make sense to smoke, but I watched a presentation on this and I'm pretty sure the main drug that is used in this manner is warfarin


----------



## Psychedelic Jay

seusemgoose said:


> I know this doesn't make sense to smoke, but I watched a presentation on this and I'm pretty sure the main drug that is used in this manner is warfarin



That is a blood thinning medicine...


----------



## seusemgoose

Psychedelic Jay said:


> That is a blood thinning medicine...






> I know this doesn't make sense to smoke,



I'm looking for the movie right now. Im positive it said warfarin even though that seems completely crazy


----------



## any major dude

Solipsis said:


> IME 500 mg is fine, but it's not right to use magnesium that also has a certain amount of calcium with it because it might defeat the purpose (not entirely sure though). I also heard you don't want magnesium oxide but don't know what it is you do want.
> 
> Bruxia appears to be the latin proper medical name and bruxism the somewhat colloquial effluent English trivial name. But I am not an M.D.
> 
> By the way I found 500 mg adequate, those huge tabs that dissolve in water with a lot of bubbles. Seemed like a good fast method of delivery and seemed to work.



thanks for the info.  I've got what look like a gigantic anti-biotic, and they are a combination of Magnesium citrate, oroate, & some other form i can't remember at the moment.  500mg worked quite well.

And that's about what I figured.  I'd always called it bruxia, but kept seeing bruxism in a number of papers etc.  Always anglicizing everything... tisk tisk America


----------



## Hammilton

He's talking about Efavirenz, a first generation antiretroviral drug which has been known to be abused for a while. There are threads already about this topic.  I didn't read the article because I don't need to.  Efavirenz is a known drug of abuse in Africa, maybe even the drug of choice among some populations.

Whether it acts as an NMDA antagonist, some sort of GABAergic (which it strikes me as- the similarity to benzodiazepines is obvious, even locates the chloro substitution in the same relative position) or something else is unknown. 

just for the record, I don't think it's a GABAergic drug, or if it is, that such activity doesn't explain the whole of it.


----------



## blauwelichten

Al jazeera is one of the more reliable news sources out there.


----------



## Hammilton

I don't think anyone denies that.  On some subjects they are certainly not in my top ten reliable sources, but overall they are quite good.


----------



## mad_scientist

Abuse of efavirenz by smoking has been known for some years, and although the mechanism of action for the CNS effects remains unclear NMDA antagonism seems likely. Probably if it was injected rather than smoked it would produce similar abusable effects while retaining its anti-HIV efficacy and being slightly less toxic than smoking pill binders...though injecting crushed pills is hardly much better!



seusemgoose said:


> I know this doesn't make sense to smoke, but I watched a presentation on this and I'm pretty sure the main drug that is used in this manner is warfarin



Actually there are cases reported of bromdifacoum (a more potent analogue of warfarin) being abused in combination with marijuana or heroin, apparently it acts as a potentiator somehow...

http://www.ncbi.nlm.nih.gov/pubmed/9111096

http://www.ncbi.nlm.nih.gov/pubmed/17022046


----------



## ebola?

The bruxism I experience is always mild, but 1000 mg magnesium consistently doesn't nothing for it (I take magnesium as a supplement pretty often anyway).

ebola


----------



## seep

There's no way that Africans are smoking warfarin or superwarfarin several times a day. At least I seriously hope not. They'd be hemorrhaging on every corner.


----------



## Cloudy

I never noticed any sort of potentiation of drugs while using warfarin. 

People will take anything to try and get high...


----------



## pharmakos

with phenethylamine psychedelics, there is typically a strong positive correlation between potency and duration.  any ideas why?


----------



## Solipsis

thenightwatch said:


> with phenethylamine psychedelics, there is typically a strong positive correlation between potency and duration.  any ideas why?




I would say if the substitution is such that it does not fit well enough in MAO to be broken down, there is much more of it to have effect so less material is needed. At the same time it is broken down slower from pharmacokinetics so duration is longer....


----------



## melange

after all these are people who kill albinos because witch doctors tell them to


----------



## melange

what is up with the para halogenated cathinones?

I bet they are even more euphoric than their amphetamine counterparts, but also neurotoxic/deadly


----------



## Solipsis

First of all it depends on which halogen, lately there have been threads on ADD about the para halogenated stimulants and the message I am still getting (also meaning I echoed what I have read in the course of a longer time without it being rejected) is that the fluoro substituted ones are the only halogen-type with acceptable neurotoxicity though how much of this is assumed or based on subjective effects (from what I understand you don't have to feel the neurotoxicity) or experiential data from lab research is unclear.

My personal opinion is that 4-FMC, 4-FA an 2-FA were all among the smoothest feeling stimulants I have tried. Euphoric but more muffled than in your face, rather sensitive and subtle, which I like. Kind of like as if there were a soft blanket over it, bk-MDMA produces this as well in me more than MDMA.


----------



## melange

from what I understand, all of the para halogenated amphetamines are neurotoxic


----------



## melange

with iodine and bromine increasing it even more than fluorine


----------



## melange

would people assume Flephedrone has more side effects than mephedrone?


----------



## pharmakos

Solipsis said:


> I would say if the substitution is such that it does not fit well enough in MAO to be broken down, there is much more of it to have effect so less material is needed. At the same time it is broken down slower from pharmacokinetics so duration is longer....



i think your logic is sound, and that is almost certainly a part of it.  however, i feel like there's got to be more to the story than that!


----------



## fryingsquirrel

thenightwatch said:


> with phenethylamine psychedelics, there is typically a strong positive correlation between potency and duration.  any ideas why?


Mescaline being the obvious exception.


----------



## i are spectre

*bupe in water*

will it decompose in water?  i've made a nasal spray, just wondering if it's stable or not.


----------



## weltschmertz

i was wondering the same. I want to delute the 8mg Bup tablets into a moonshine (alcohol 55%).
I know is highly solvent in alcohol,but please some one tell how much alcohol ex. per 5 pills.


----------



## pallidamors

Pretty sure it doesn't in any appreciable amount. It's not like heroin in that way. I'm pretty sure some BLers pretty much do the same thing as you with their bupe to titrate their doses.


----------



## Morphoid

I tried this earlier this year with suboxone and created a solution 2mg buprenorphine to 2ml sterile water and it worked fine after a couple of weeks, suggesting that there wasn't much decomposition. Naloxone is highly soluble in water but as bupe has a much higher affinity it's not worth thinking about.


----------



## zero zero

Is N N dimethyllysergamide psychedelic when injected. Does this thing work like tryptamines. Are there any reports.


----------



## Captain.Heroin

i are spectre said:


> will it decompose in water?  i've made a nasal spray, just wondering if it's stable or not.



Yes, it is stable.  I have made a buprenorphine solution and used it over the course of a month.  This is why Buprenex is not a dry ampule like diamorphine ampules in the UK are.


----------



## melange

the guy that started the now closed thread on putting 25i-NBOMe on blotter creeps me out


----------



## Hammilton

melange said:


> from what I understand, all of the para halogenated amphetamines are neurotoxic



No, they're certainly not all neurotoxic; it seems that only the bare para-halo-amp's are (excluding 4-FA, again) neurotoxic, and that the halogenated amphetamines DOI, DOC, DOB, and the like are not neurotoxic.  It could be that because they are so potent they're never taken in doses that would have a substantial effect on monoamine transport and release, but I don't know for certain if that is the case.

While 4-FA and perhaps 4-fluoro-methcathinone are not neurotoxic, I wouldn't consider them safe.  fluoro is not the same as trifluoromethyl, obviously, but I would worry about 5HT2b agonism.

Actually, all of those morons taking huge doses of mephedrone for days at a time should be incredibly concerned about potential 5HT2b agonism.  There are bad things- panic attacks, depression- and then there are _bad_ things like cardiac arrest.


----------



## melange

Hammilton said:


> No, they're certainly not all neurotoxic; it seems that only the bare para-halo-amp's are (excluding 4-FA, again) neurotoxic, and that the halogenated amphetamines DOI, DOC, DOB, and the like are not neurotoxic.  It could be that because they are so potent they're never taken in doses that would have a substantial effect on monoamine transport and release, but I don't know for certain if that is the case.
> 
> While 4-FA and perhaps 4-fluoro-methcathinone are not neurotoxic, I wouldn't consider them safe.  fluoro is not the same as trifluoromethyl, obviously, but I would worry about 5HT2b agonism.
> 
> Actually, all of those morons taking huge doses of mephedrone for days at a time should be incredibly concerned about potential 5HT2b agonism.  There are bad things- panic attacks, depression- and then there are _bad_ things like cardiac arrest.




I see


and agreed with the 5HT2b agonism topic

scary stuff there

there is a reason I quit taking daily 5-htp a long time ago


----------



## ebola?

> would people assume Flephedrone has more side effects than mephedrone?



Yes, but it's likely that they would be mistaken.
4-fluoro-amphetamine has been demonstrated non-neurotoxic, in the same way that bk-mdma was demonstrated non-neurotoxic, in contrast to mdma, the latter cast as mildly neurotoxic.  White 4-methyl-amphetamine has not been as rigorously studied for such activity, anecdotes suggest that it leaves inordinately long-lasting mental effects.

As for cardiovascular side-effects, there is no clear evidence that 4-fluoro-ephedrine would be much better or worse than 4-methyl-ephedrine.

ebola


----------



## Lombergerh

I have some sort of silly questions again:
Is it possible to produce benzodifuran analogs of DOM / DOI / DOC etc?
And is it possible to apply similar techniques to tryptamine?
Maybe NBOMe-tryptamines or benzodifuran-tryptamines?

PS I hear that syntesis of FLY analogs is the most expensive, is it true?


----------



## Astavats

Lombergerh said:


> Is it possible to produce benzodifuran analogs of DOM / DOI / DOC etc?



Yes; I'm pretty sure Iodo-dragonFLY has been studied, or a similar relative.



Lombergerh said:


> And is it possible to apply similar techniques to tryptamine?
> Maybe NBOMe-tryptamines or benzodifuran-tryptamines?



Benzo*di*furan wouldn't work on tryptamines, unless you change it from a indole to a benzodifuran body by replacing the nitrogen with an oxygen. However this replacement of nitrogen with oxygen leads to less effective activity at the 5-HT2A site. You could add a furan ring to a tryptamine psychedelic however tryptamines and phenethylamines do not dock the same way thus there is no promise of it playing out as effectively. N-benzyl series could be applied to tryptamines though again considering they do not dock the same way there is no certainty of it being an improvement. I can't recall if this has been done before.


----------



## Hammilton

IIRC it has but produces only minor improvements, unlike the 200x improvement seen with 2C-C


----------



## arez00

*modafinil*

i read alot of article about modafinil and i found if we replace amine group with n-aryl, the activity of drug change to sedative(like piperidine), do you know why, and have you ever seen a compound to ignore this comment?


----------



## arez00

*synthesis of modafinil*

do you know what is the difference between the activity of modafinil and the same compound without the oxidizing sulfor? i want to found how much this functional group are important in cns activity of drug, because the oxidizing sulfor need a difficult sittuation like the degree under 20 to prevent make sulfon.


----------



## MurphyClox

arez00 said:


> i read alot of article about modafinil and i found if we replace amine group with n-aryl, the activity of drug change to sedative(like piperidine), do you know why, and have you ever seen a compound to ignore this comment?


There is no amine in modafinil, but only an ami*d*e.
And the reason why replacement of the amide moiety -C(O)NH2 with -C(O)N(CH2)5 (i.e. piperidine) leads to sedative derivatives (as reported in _EP_ 0097071 A1 or _Bioorg Med Chem_ *2008*, 16, p.9904) is not known to my best knowledge, at least not in the peer-review literature.
And by the way, the mechanism by which modafinil reaches its biological effects is currently not known with certainty at all. Much speculation here, but hardly any viable SAR to play with.



arez00 said:


> do you know what is the difference between the activity of modafinil and the same compound without the oxidizing sulfor? i want to found how much this functional group are important in cns activity of drug, because the oxidizing sulfor need a difficult sittuation like the degree under 20 to prevent make sulfon.


The last part I didn't understand completely...

The sulfone-analog of modafinil was shown to have almost the same activity like modafinil itself, shown with mice in a maximum electroshock assay (_Bioorg Med Chem_ *2004*, 29, p.1481). Don't know how this one translates into stimulating activity in humans though, but I'd be really careful with preliminary conclusions. Toxicity was in the very same range, too, like modafinil.


Peace! - _Murphy_


----------



## Solipsis

As in low toxicity right? Or I'd better do my modafinil homework again. I do like the stuff, for its non-addictive properties (at least found by me) and that it doesn't really stimulate but achieves unparalleled wakefulness nonetheless. And still, it's not a disaster when you try to sleep.

About the similarity with sedative compounds, might this have something to do with the possibility of paradoxical effects that modafinil can have i.e. some people have to run for their beds after taking it! And one time I got mega drowsy from it as well.


----------



## MurphyClox

Yeah, modafinil's acute toxicity is comparably low.


----------



## literate

Alpha-hydroxymethylphenethanamine and N-methyl-alpha-hydroxymethylphenethanamine are commercially available, but are they psychoactive?

My guess is that they are both stimulants with a shorter duration of action than their amphetamine analogues, as the hydroxymethyl group would be metabollized to the carboxylic acid rather quickly.  And since each has only one -OH group per molecule, they should both pass the blood brain barrier rather easily.


----------



## seep

literate said:


> N-methyl-alpha-hydroxymethylphenethanamine



plausible meth precursor & positional isomer of ephedrine. No info on psychoactivity.


----------



## Solipsis

About that last question: it depends on the absorption but anything that gets absorbed subligually or buccally or whatever follows a parenteral route and should therefore potentiate your dose compared to oral administration, but that completely depends on the bioavailability though these different RoAs.

AFAIK alpha-(de)methylation is not done very easily?


----------



## Slapdragonx

The PiHKAL synthesis for DOI and 2C-I start with 2,5-DMA (2,5-Dimethoxyamphetamine)and 2C-H (2,5-Dimethoxyphenethylamine).

So I would assume that it would be pretty hard to do.


----------



## melange

ebola? said:


> in the same way that bk-mdma was demonstrated non-neurotoxic



do you have a references for this?

I am genuinely curious, as methylone is a lostlove/vice of mine.


----------



## drugs

How hard is 3-meo-pcp to synth? Does it take some highly skilled individual to do this? Im leaning more towards chinese 'chemists' just plain sucking?


----------



## Solipsis

I don't know if you can just do it the same as 4-MeO-PCP only substitute a certain brominated reagent (let's not get into specific synth discussion, it's not allowed), but I think I heard it's mostly more expensive to make - possibly because of the price of that ingredient.


----------



## Astavats

*Question*: Is there a 'endogenous cannabinoid "releasing agent"'?

I'm not certain how else to state the question. From what I've understand trying to get the answer endocannabinoids aren't stored in vesicles so "releasing" might be incorrect term. Is there any drug that activates biosynthesis of endocannabinoids? Does anyone know if there are any in Cannabis?

If someone can direct me to such compounds(s) or literature discussing this I would appreciate it.


----------



## melange

I think this will remain mysterious my friend(for now)

just like kappa opioid "releasers"

and dmt agonists


----------



## toriath1

can i shoot phentermine hydro clorride 37.5 ml pills????????


----------



## melange

technically please use a micron filter


----------



## toriath1

melange said:


> technically please use a micron filter


lol im sorry man i dnt kno wtf that is.... where do i get it? im feenin


----------



## dread

toriath1 said:


> can i shoot phentermine hydro clorride 37.5 ml pills????????



why the fuck would you even want to do something like that.


----------



## toriath1

dread said:


> why the fuck would you even want to do something like that.



cuz im a junkie. so help or shut the fuck up. i didnt come to get counceling


----------



## ebola?

. . .nor did you come to make appropriate posts in here. 
Please give Other Drugs a try, and make sure to run a search before asking your question.

ebola


----------



## Slapdragonx

You could inhibit the metabolization of the endogenous cannabinoids (specifically Anandamide) by using a FAAH inhibitor.

N-acylphosphatidylethanolamine (NAPE) or phosphatidylethanolamine will increase the amount of Anandamide synthesized versus using a FAAH inhibitor. Or you could do both.

But there is no such thing as an endocannabinoid releaser. Arachidonic acid is the raw basis of NAPE and it is healthy and is commonly used as a bodybuilding supplement (fatty acid).


----------



## Astavats

Again I say "releaser" for lack of a appropriate term. I'm aware of enzymatic way of enhancing concentration but I was hoping for a "biosynth. activating" route. 

I guess I'll take that answer then, thank you Slapdragonx.


----------



## Slapdragonx

The precursors to Anandamide (and other endogenous cannabinoids) are NAPE (as noted above) and Arachidonic acid - AA. With the precursors you would probably see a mild increase in the amount of endogenous cannabinoids produced within the body.

Unless you are speaking of something that directly stimulate the production of endocannabinoids, in which case I have no clue.


----------



## Astavats

Yes I meant telling the brain to produce more not increasing concentration with biological precursors. I was hoping someone would know a direct or indirect (ie. activation/inhibition of non-CB receptor leading to this) method of doing this.


----------



## Slapdragonx

Technically you can activate CB1 via the allosteric binding sites and increase the concentration of the endocannabinoids. However at the same time they decrease the activity of the agonists.

Such as 1-(4-chlorophenyl)-3-(3-(6-pyr​rolidin-1-ylpyridin-2-yl)pheny​l)urea (PSNCBAM-1) or SR141716A (Rimonabant).

PSNCBAM-1:


----------



## Astavats

That's interesting and gives me something to read into now. Thank you for your time Slapdragonx!


----------



## DLS Services

http://en.wikipedia.org/wiki/Whoonga

From what I've read it sounds like dealers are just cutting heroin with a bunch of shit to get more money.


----------



## P A

> just for the record, I don't think it's a GABAergic drug, or if it is, that such activity doesn't explain the whole of it.



Either way, it looks like it (and nevirapine, another reverse transcriptase inhibitor with a 1, 4-diazepine core; not sure if that's of any significance) _has _ had words with some overactive NMDA receptors in a few studies. I thought this was a pretty good read:

http://eprints.ru.ac.za/1350/1/Zheve-MSc-TR08-169.pdf

Not that it's necessarily relevant - it could just as easily be a bunch of  placebo-sodden, virus-free South African drug users who take desperation to darkly comical heights. One would think the side effects of megadoses of the RTIs would far outweigh a transient placebo high. I wonder if there's a hangover...



> this sounds similar to the tamiflu story I read about a while ago



Lawl, yeah. That and jenkem.


----------



## Hammilton

> it could* just as easily *be a bunch of placebo-sodden



No, it couldn't "just as easily" be placebo effect.  I once found a document talking about placebo effect and psychoactive drugs but I can't seem to find it.

People don't become hooked on placebo.  Placebo effect is invariably weaker than actual drug effect, and produces substantially different responding.  People have passed off fake drugs as real all the time, and at others rumors would go around about how this or that would get you high.  People realize they've been sold garbage.  For short periods of time kids will start smoking oregano or grass or snort tylenol, but people try it, and realize they've been stupid, and so they never catch on.

this has caught on.  So either it's an incredible outlier, or the drugs are active.  No matter what though, the odds that this drug is actually not recreational are very, very small.


----------



## hamhurricane

I know this has been posted before (I believe by Vecktor) but I cannot seem to find it, does anyone have a link to a key or guide or journal article of some kind that gives a rough estimate of how to extrapolate human doses from animal data, specifically mice and rats?


----------



## P A

> People don't become hooked on placebo



Sure they do, so long as the reinforcement schedule is intermittent. These people obviously aren't regularly ingesting the substance at specified intervals in controlled dosages, as would be expected therapeutically. And since the drug _is_ a definite neuroactive substance, it could very easily be something of an "active placebo" in such a case as this. 



> For short periods of time kids will start smoking oregano or grass or snort tylenol, but people try it, and realize they've been stupid, and so they never catch on.



That's a tad overly facile, don't you think? Couldn't it have more to do with to do with sudden realization of what constitutes 'true' or 'genuine' psychoactivity? That is, following the inhalation of some burning plant matter that actually contains psychoative compounds, these impressionable oregano-heads come to realize what they'd been, so to speak, missing, and subsequently abandon their useless euphoric modalities (lulz). And sure, the placebo effect does tend to be highly susceptible to extinction in most cases, but many claim to have been using homeopathic remedies (and the like) for years, engendering unyielding symptomatic improvement. Inert drugs _are _ generally less successful than their active counterparts on the black market, but I think this owes more to the relative magnitude of effect (and the subsequent word-of-mouth broadcasting that the shit is bunk) and the heightened discriminative prowess of seasoned drug abusers as compared the other, more chemically naive consumer-base of dumb, inexperienced kids (and, as the case may be, South African adults).



> either it's an incredible outlier, or the drugs are active



Agreed, they're definitely active, just more than likely non-recreational.


----------



## Hammilton

> That's a tad overly facile, don't you think? Couldn't it have more to do with to do with sudden realization of what constitutes 'true' or 'genuine' psychoactivity? That is, following the inhalation of some burning plant matter that actually contains psychoative compounds, these impressionable oregano-heads come to realize what they'd been, so to speak, missing, and subsequently abandon their useless euphoric modalities (lulz). And sure, the placebo effect does tend to be highly susceptible to extinction in most cases, but many claim to have been using homeopathic remedies (and the like) for years, engendering unyielding symptomatic improvement. Inert drugs are generally less successful than their active counterparts on the black market, but I think this owes more to the relative magnitude of effect (and the subsequent word-of-mouth broadcasting that the shit is bunk) and the heightened discriminative prowess of seasoned drug abusers as compared the other, more chemically naive consumer-base of dumb, inexperienced kids (and, as the case may be, South African adults).



No, it's not.  Actually, if anything, your argument is based on lack of thought.  Did you even decide to look at research before coming to your conclusion?  Apparently not.  More than 50% of patients taking efavirenz report CNS effects.  Slightly more than 25% of patients receiving placebo reported CNS effects.  These were at prescribed doses, though.

More than that, your last point is based on the supposition that South Africans don't have access to good drugs.  There's no question about the inaccuracy of that point.  South African drug users are no more limited than we are.  They may have less cannabis (not much less though, it's still the second most commonly abused drug, next to alcohol), but they have easy access to most pharmaceuticals.


----------



## P A

> No, it's not. Actually, if anything, your argument is based on lack of thought.



If anything, your counterargument is based on a serious lack of reading comprehension. Did you even decide to read my post before concluding that I had disagreed?

Taken directly from said post:



> *And since the drug is a definite neuroactive substance, it could very easily be something of an "active placebo" in such a case as this.*



and



> *Agreed, they're definitely active, just more than likely non-recreational.*





> More than 50% of patients taking efavirenz report CNS effects. Slightly more than 25% of patients receiving placebo reported CNS effects



As I can only hope you've noticed after, you know, actually reading what I typed, you're not doing yourself any justice by vehemently disputing the barely contentious comments of someone whose opinion lies in essential accordance with yours (aside from a minor point of whether the drug truly is a genuine reinforcer), and was simply trying to spur further discussion. I think the expression is 'preaching to the choir,' or something to that effect.



> More than that, your last point is based on the supposition that South Africans don't have access to good drugs



...no. It's based upon the assumption that the vast majority of 'recreational' efavirenz users_ in particular_ are either pharmacologically naive, desperate for a high, or are simply experiencing a collective phenomenon of positive response to an active placebo. That's all.


----------



## fryingsquirrel

If it's being used to cut heroin I would say the heroin has far more likely to be what is making this recreational than either placebo affect or efavirenz.


----------



## Captain.Heroin

toriath1 said:


> lol im sorry man i dnt kno wtf that is.... where do i get it? im feenin



Micron Filtering Mega Thread & FAQ

Try reading the entire first post, and the FAQ section.


----------



## asecin

lol i love this thread. basically the moderators have a sense of trollism in them and decide to troll hard working thread providers with a bunch of crappy gather-it-all-in thread. 

epic


----------



## melange

^owned


----------



## reformer

*N-Acetylation of the 2C-X series... Impacts activity?*

Does anyone know where I can find info to determine whether N-acetylation of the 2C-X Shulgin series will impact activity?

From the scant precedents I found, it would appear that ephedrine retains activity after N-Acetylation, but on the other hand mescaline loses activity.

I tried in PiHKAL, to no avail (but I cold have missed it)...

So, N-Acetylation of the 2C-X series will likely improve absorption into body and across BBB... but will it decrease activity? 

Any help? (sources of info or subjective opinions)


----------



## mycotoxin

Has anybody ever made morphine from codeine and then turned it into diacetylmorphine?
I'd like to have a go as long as it can be done cheaply....How much would all the equipment/chemicals set you back to get set up (AND IF ANY COPS ARE READING THIS, ITS PURELY FOR REASEARCH PURPOSES AND IM ONLY ENQUIRING FROM PEOPLE WHO HAVE DONE IT BEFORE FOR PERSONAL USE, AS I DONT THINK ITS POSSIBLE TO DO THIS ON A LARGE SCALE ANYWAYS)
Are we talking £100? £500? £1K plus? Surely all you need is a few pieces of laboratory equipment (bunsen burner, some kind of filtration/extraction device, boiling/test tubes etc) and the chemicals (Pyridine,chloroform etc. - Which I'm told are fairly cheap anyway) and I'm reckoning about £50 worth of codeine based painkillers maybe! lol! I'm making a guess here and saying you could probably get all this stuff for a couple of hundred quid maybe? Any chemists know the answer?


----------



## ebola?

We do not allow synthesis discussion in any of our forums; please review our guidelines.

ebola


----------



## dread

> few pieces of laboratory equipment (bunsen burner, some kind of filtration/extraction device, boiling/test tubes etc)



Let me tell you straight out: you have no chance at making heroin from codeine. Just forget it before you get yourself hurt.


----------



## asecin

hi guys can i make heroin from cocaine ?


----------



## avrolling

*Looking for a foot in the door.*

Hey guy's I've been looking at your post's and am extremely entrigued, I was wonder if maybe someone could maybe teach me some things?      Thanks


----------



## Astavats

Try these stickied threads Erowid/BlueLight Neuropharmacology Text and The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread, combined they contain quite a bit of information from introductory to very advanced.



avrolling said:


> maybe someone could maybe teach me some things?



Lesson: Asking specific questions will lead to better responses.


----------



## Transform

Enroll into some classes about pharmacology, or perhaps biology or chemistry. It'll be your easiest (and probably best) way to learn, and if it interests you then you're likely to do well without too much struggle.


----------



## AlphaMethylPhenyl

Hammilton said:


> You think anyone would risk jail time to help you kill yourself?
> 
> And I thought I had a big ego.



You do but witty comments like that help make up for it.


----------



## asecin

ok so still no ideas ? hmm how about i synthesize marijuana from oregano


----------



## fryingsquirrel

asecin said:


> hi guys can i make heroin from cocaine ?


No, but you can make crack from heroin. It looks like tar for some reason. Sometime you give the guy the cash and instead of the usual shit you get the black, heroin based crack.


----------



## ebola?

cease and desist.


----------



## Vader

> Let me tell you straight out: you have no chance at making heroin from codeine. Just forget it before you get yourself hurt.


Really? I was under the impression that "homebake heroin" was relatively easy to produce.


> The patterns of drug abuse found in New Zealand (NZ) are influenced by the fact that it is a geographically isolated country with a small population (3.3 million). One recent feature has been the emergence of small-scale illicit laboratories producing morphine and heroin from codeine derived from commercially available codeine-based pharmaceutical products. This paper describes the background to this development, the methods used in such laboratories, and the approach taken by the forensic scientist in examining them...
> Codeine, in certain compound products is not controlled under the NZ Misuse of Drugs Act (1975) and is available without prescription from retail pharmacies. The first laboratory using the process was seized in Auckland in January 1983. In the three years which followed to January 1986, Auckland police alone seized over 50 such laboratories, either fully functional or as disassembled 'kits', and over 90 were seized in NZ as a whole. Laboratories have been encountered in kitchens and bathrooms in most parts of the country. The home-made product of this simple recipe-like procedure has become known as 'homebake'. The equipment required for these laboratories is very simple and the product is normally made in small batches for the addict's own use, although there has been a trend towards the sale of samples of the end product.


Can't post the link because it's synth discussion but PM me if you want and I'll send it to you.


----------



## ebola?

The liver catabolizes codeine into morphine in vivo, and yeah, reaction of morphine into heroin in vitro is pretty trivial.  As to whether the first reaction is viable in vitro, just with kitchen chemistry, is another story.

ebola


----------



## Vader

^The fact that so many junkies manage to do it makes me think that it probably is viable. Probably not a very good idea, given that the reagents are highly toxic, but feasible.


----------



## dread

The point I was trying to make is... if he has to post in here asking things like "how much does it cost" and "what kind of equipment do I need" then it's pretty clear that he does not have the qualifications necessary to perform the chemistry.


----------



## negrogesic

Read, read and.........read. Though formally educated I am a true autodidact, I learn things in my own way........sometimes with dire consequences............


----------



## Peter_from_Zurich

I already asked for my old thread contents.
Meanwhile i'll try to make a good excerpt to reconstruct them here.
If you want me to move it just let me know.


----------



## 23536

I thought pyridine was a watched chemical.  Didn't it used to be in one of the lists?


----------



## stumblestoprepeat

Where would be a good place for a beginner to learn the basics of (neuro)pharmacology? i.e. the different receptors/how they work/SR/DA systems, that kind of thing. Online or textbook suggestions are most appreciated.
I know taking a college course would be preferable, and that's coming in due time, but I'm trying to get a good intro on the material until Fall2011 at which point I will be enrolling in a bio class.


----------



## melange

I have a silly question.


So for example people say don't take an ssri with another ssri because of serotonin syndrome. But in actuality, the one with the higher binding profile would win out? Right? Why do they say this? Do they potentiate each other?


----------



## amanitadine

235360287471352662 said:


> I thought pyridine was a watched chemical.  Didn't it used to be in one of the lists?



It is not a listed precursor or "essential" chemical in the U.S. It _might_ attract some scrutiny for its use in demethylation or for conversion to piperidine but its sale is not regulated. I think it is on the "suspicious" chemicals list but so are 500 other things. I certainly never had any problem.


----------



## melange

melange said:


> I have a silly question.
> 
> 
> So for example people say don't take an ssri with another ssri because of serotonin syndrome. But in actuality, the one with the higher binding profile would win out? Right? Why do they say this? Do they potentiate each other?



anyone? nuke, vecktor?


----------



## amanitadine

t I don't think that normal doses of SSRIs would saturate occupancy by ANY stretch so it would reason that the effects would be additive. But I can't see simple reuptake inhibition alone causing Serotonin Syndrome.


----------



## ebola?

I believe that it can in massive overdose.


----------



## tamtoot

Can anybody tell me for how long a1-adrenergic receptors are downregulating to the "normal" level. I'm asking for how long somebody who use nasal drops will have blocked nose when withdrawing cold turkey. I have searched, but found only basic info on adrenergic system and no any info on the lifecycle of receptor.
Thank you.


----------



## Transform

My girlfriend was totally hooked to the xylometazoline sprays, we bought her a full bottle and then topped it up every day with distilled water so the doses gradually became less and less to help her taper. Took a good month but she is free now.


----------



## ragemaxis

I remember having a pre-tihkal times book that talked alot about tyramine,  I guess its in alot of foods and fairly easy to synthesize,   what a drug though,   its kind of like inducing the dopesicks except without the high before.


----------



## tamtoot

Transform said:


> My girlfriend was totally hooked to the xylometazoline sprays, we bought her a full bottle and then topped it up every day with distilled water so the doses gradually became less and less to help her taper. Took a good month but she is free now.



I also made her titrated solution, but she decided to kick it cold turkey.


----------



## nuke

melange said:


> anyone? nuke, vecktor?



The contraindication is less for serotonin syndrome and more for the unpredictability of mixing psychiatric medications and for the likeliness of overdosage from combination.  While the one with a higher binding affinity would reside in the transporter longer, having higher concentrations of both drugs in the brain would lead to higher occupancy in general (that is, the maximal dosage of the drug would decrease, possibly unpredictably, when combined with another drug with similar action).


----------



## asecin

ragemaxis said:


> I remember having a pre-tihkal times book that talked alot about tyramine,  I guess its in alot of foods and fairly easy to synthesize,   what a drug though,   its kind of like inducing the dopesicks except without the high before.




ragemaxis sup pal. didnt know you visit this place :D


----------



## Vader

Q:


> Where would be a good place for a beginner to learn the basics of (neuro)pharmacology? i.e. the different receptors/how they work/SR/DA systems, that kind of thing. Online or textbook suggestions are most appreciated.
> I know taking a college course would be preferable, and that's coming in due time, but I'm trying to get a good intro on the material until Fall2011 at which point I will be enrolling in a bio class.


A:
BL Neuropharmacology Text
Right under your nose (it's the sticky beneath this thread in ADD).


----------



## arez00

*affect of phenobarbital on modafinil*

Hi, how long does it take that phenobarbital induce liver enzyme? i want gavage modafinil after adminstration of phenobarbital in rat. does it change concentration of modafinil just in first dose?


----------



## the outsider

If MDA is a metabolite of MDMA, does it follow that the effects of MDMA are in part those of MDA as well?

I'm not too clued-up on my pharmacology.


----------



## Transform

Yes, although MDA is a minor metabolite, most MDMA is excreted unchanged, so while there might be a hint of MDA, it won't be significant.


----------



## roddy

Sturnam said:


> What exactly does the "nor" prefix mean? Is it simply a dealkylated version of the original? Does it mean that it always comes off of the amine group?


all it means is a nitrogen has had an alkyl removed.


----------



## ebola?

Right.  It stems from "No R", signifying the removal of a substitution from a particular skeleton.

ebola


----------



## ...

^That etymology is as false as the "no ohne radikal" etymology, but I like it.


----------



## ebola?

Lol, my mistake.  Most etymologies in dictionaries are actually false, so I don't feel that bad.

ebola


----------



## Hyperthesis

This could be helpful: http://en.wikipedia.org/wiki/Nor-


----------



## radric davis

*Octopamine*

While researching nuerotransmitters I found Octopamine. Apparently its mainly found in invertebres but has been given to humans under a variety of names and stimulates the sympathetic nervous system. Does anyone know more about the specific effects of Octopamine?


----------



## nuke

Yes.  It is used by bodybuilders and apparently not much fun.  Search their forums. 

Or, perhaps even search our forums:
http://www.bluelight.ru/vb/showthread.php?t=322626&highlight=octopamine



> I knew about octopamine in August of 2000.
> 
> At that time, all of the human studies (and there were very few) showed beta 3's not to work (the rat studies were great though). In addition, an in vitro study specifically with octopamine did not produce results in human adipose tissue (though, it was great in rats).
> 
> I also asked Elzi Volk, who has done more research on the adrenergic system than anyone in the bodybuilding world, and also communicates with a lot of researchers, and it was her opinion that they would not do anything in humans. She already knew about octopamine at that time, BTW.
> 
> However, there was a recent human study with a beta 3 that showed it to be somewhat effective, so WTF knows.
> 
> The important thing is that all rat data on beta 3's and fat loss/lipolysis is MEANINGLESS, as humans and rats have very different adrenergic systems. And, you can guarantee they will toss rat studies out as evidence, just as they did with norephedrine.


http://forum.bodybuilding.com/showthread.php?t=31321


----------



## Freakybass

*Vaporization : Difference between melting and boiling point*

It is still unclear to me which point refers to the vaporization temperature.
By reading the forum posts, people sometimes refers to the _melting point_ to know the vaporisation temperature of a compound and sometimes the _boiling point_.

Does anybody know what information (melting or boiling) is relevant to know the "vaporization temperature" of a psychoactive compound in terms of inhalation ?


----------



## sekio

The boiling point? Although a lot of chemicals decompose at boiling, and the boiling point depends on the pressure of the environment in question.

How is this advanced drug discussion? Melting isn't boiling?


----------



## Freakybass

sekio said:


> Although a lot of chemicals decompose at boiling


Could you please elaborate ? By giving an example for instance.



sekio said:


> the boiling point depends on the pressure of the environment in question.


Yes I know. But usually in the chemical data sheet, the pressure given.
Sorry to haven't write it clearly in my first post.



sekio said:


> How is this advanced drug discussion? Melting isn't boiling?


I think you didn't clearly understand my question. It was the last sentence of my post :
_what information (melting or boiling) is relevant to know the "vaporization temperature" of a psychoactive compound in terms of inhalation ? _


----------



## atara

Well, substances usually achieve a substantial vapor pressure somewhat below their boiling point. A vapor pressure of 20 kPa is all that is necessary to smoke something -- 101 kPa is boiling.


----------



## allium

Guys, 5-methoxy-tryptamines give me some strange "sweet", "sugar" feeling in my head. I am wondering if it can be related to 5-HT1a receptor agonism. Where can I find some data on them? 
Chart(like one below) would be nice to see, but plain text data is ok too. 






Also, it would be nice, if someone answer this question: why 5-MeO-T's produce so less visuals(if any)?


----------



## Solipsis

Doesn't also depend on the general stability of the compound, how easily it pyrolyses/oxidizes? If it's pretty stable then I don't see why you cannot just go well above the boiling point and vaporize it decently. If it is less stable then it is probably better to stay júst under the boiling point so that it doesnt vaporize like crazy and handles the excess heat badly.
Does that make sense?

The boiling trajectory of freebase DMT for instance is 60-80 degrees Celsius right? So if you have an electric vaporizer you should set it to somewhere around 65?


----------



## any major dude

OK, so i've been looking around using both the BL search engine and google's site search as i'm sure this is somewhere on BL, but for the life of me i can't find it.  Anyway, is it possible to remove the levo-amphetamine from adderall type mixtures?  And if so, how, if it is feasible to do with limited equipment etc.  Sorry if there's a thread on this somewhere obvious, but i'm tapped out of search terms to attempt to locate said info.


----------



## Freakybass

I agree for the DMT freebase.

But for the cocaine freebase for instance, I see every on Internet the melting point for the vaporisation issue.
Even Erowid mention this :


> However, the salt form of many compounds has a much higher *melting*/vaporization point than the freebase (or freeacid if its got an acidic group instead of the basic amine group).


http://www.erowid.org/ask/ask.php?ID=2348

Do you think it's a mistake ?


----------



## atara

The slash there indicates "and", not "or".


----------



## nuke

allium said:


> Guys, 5-methoxy-tryptamines give me some strange "sweet", "sugar" feeling in my head. I am wondering if it can be related to 5-HT1a receptor agonism. Where can I find some data on them?
> Chart(like one below) would be nice to see, but plain text data is ok too.



http://pdsp.med.unc.edu/pdsp.php


----------



## nuke

any major dude said:


> OK, so i've been looking around using both the BL search engine and google's site search as i'm sure this is somewhere on BL, but for the life of me i can't find it.  Anyway, is it possible to remove the levo-amphetamine from adderall type mixtures?  And if so, how, if it is feasible to do with limited equipment etc.  Sorry if there's a thread on this somewhere obvious, but i'm tapped out of search terms to attempt to locate said info.



Use tartaric acid as specified in paragraph 4: http://www.erowid.org/archive/rhodium/chemistry/amph.cth.ppa.html


----------



## ...

nuke said:


> Use tartaric acid as specified in paragraph 4: http://www.erowid.org/archive/rhodium/chemistry/amph.cth.ppa.html



I don't think racemic tartaric acid will lead to anything but a racemic mixture.


----------



## nuke

... said:


> I don't think racemic tartaric acid will lead to anything but a racemic mixture.



That should be a given, you should be able to figure out which to use...

The CAS number (3994-11-4) specifies dextrotartaric acid for d-AMP in a (1:2) proportion


----------



## melange

nuke said:


> That should be a given, you should be able to figure out which to use...
> 
> The CAS number (3994-11-4) specifies dextrotartaric acid for d-AMP in a (1:2) proportion



no shit


----------



## I Eat Pho

*Ether substitute (as a solvent)*

Hello,

I've been trying to do some research around what solvents would be the best substitute for ether as a solvent with the following properties.  

Would Cyclopentyl methyl work?

Appreciate any help.


----------



## any major dude

thanks a bunch for the information!  also stumbled across this http://www.erowid.org/archive/rhodium/chemistry/amphetamine.resolution.html


----------



## Iodjini_dk

Do you mean methylcyclopentane? If so I guess it would work as a non polar solvent. Otherwise pentane would also be suitable. But the best choice of solvent depends on what you want to dissolve


----------



## Hammilton

maybe cyclopentylmethane


----------



## I Eat Pho

Thanks, 

This would be to dissolve coca paste.  I understand that the critical factors for a non-polar solvent substitute are:

a) Solubility of coke base
b) Miscibility with acetone +hci
c) insolubility of cocaine hci in the combined mixture of the ether substitute acetone/hci


----------



## 23536

THF

btw "hci" = hcl


----------



## nuke

235360287471352662 said:


> THF
> 
> btw "hci" = hcl



THF is miscible in water (like dioxane) and is heavily watched

Chloroform works for some applications


----------



## I Eat Pho

Is Chloroform not watched? I thought it was.


----------



## Iodjini_dk

Some simple alkane would maybe do the trick. Hell, they use gasoline in Latin America for extraction of the freebase


----------



## vortex30

I Eat Pho said:


> Is Chloroform not watched? I thought it was.



It may be, but as I understand, it is also quite easy/cheap to synthesize yourself. Correct me if I'm wrong, I just remember a friend of mine wanting to do it for kicks and he had no formal chemistry training over the high-school level. He was extremely knowledgeable though. His dad did own some pretty nifty machines, so perhaps he intended to use one of those, which would make the synthesis dependent on having access to expensive equipment...


----------



## Vader

^No specialist equipment is needed, it is very easy, you can do it accidentally.


----------



## nuke

This is correct, there is an article on Erowid about its facile synthesis...  It works very well for many but not all alkaloids and has a low boiling point so it dries very quickly (in fact, you can boil it on a hot plate in a hood if you like to dry off your product, so long as the product doesn't decay at 60C).


----------



## hamhurricane

I was thinking about _The Ryan Haight Act_ and _Brett's Law_ and wondering if anyone can think of other laws that were enacted because of the death of a teenager? I know OpWebT was largely the result of some teen overdoses but what about in the more distant past...can anyone think of examples?


----------



## ---

has it been established that mdpv is mostly dopaminergic? at least two people agreed with that in the eadd mdpv thread, but many others have said there is far more adrenalin than dopamine in the mdpv experience, and that goes in line with my experience as well.


----------



## ch3mist

vortex30 said:


> It may be, but as I understand, it is also quite easy/cheap to synthesize yourself. Correct me if I'm wrong, I just remember a friend of mine wanting to do it for kicks and he had no formal chemistry training over the high-school level. He was extremely knowledgeable though. His dad did own some pretty nifty machines, so perhaps he intended to use one of those, which would make the synthesis dependent on having access to expensive equipment...



Halogenation of an alkane is one of the first reactions you tend to see a mechanism for in a college Organic I lecture, and there's a really good reason why. You start simple.


----------



## Vader

How do chemists discover drugs that are unrelated to a natural lead compound? How did, for instance, PCP or pethidine come to be created, and how was it deduced that they might be pharmacologically active? I'd just like to know how any drug is invented in a "revolutionary", rather than "evolutionary" way, without being based on SAR or rational design or anything.


----------



## 23536

Yerg said:


> How do chemists discover drugs that are unrelated to a natural lead compound? How did, for instance, PCP or pethidine come to be created, and how was it deduced that they might be pharmacologically active? I'd just like to know how any drug is invented in a "revolutionary", rather than "evolutionary" way, without being based on SAR or rational design or anything.



Lednicer explains the genealogy of both in volume I (pages 56 and 299). Both were engendered by SAR.

As for pure serendipity: the story of LSD is well known, as is that of penicillin.


----------



## 23536

hamhurricane said:


> I was thinking about _The Ryan Haight Act_ and _Brett's Law_ and wondering if anyone can think of other laws that were enacted because of the death of a teenager? I know OpWebT was largely the result of some teen overdoses but what about in the more distant past...can anyone think of examples?



he was twelveteen, but Len Bias' death was HUGE as far as laws go.  Possibly tens of millions of African American men are in prison today because society decided to protect them from cocaine (I'm referring specifically to the series of mid-1980's laws that, among other things, affixed a hundredfold multiplier to crack sentencing)

I think also New York's Rockefeller Laws were inspired by the death of a person.


----------



## asecin

vortex30 said:


> It may be, but as I understand, it is also quite easy/cheap to synthesize yourself. Correct me if I'm wrong, I just remember a friend of mine wanting to do it for kicks and he had no formal chemistry training over the high-school level. He was extremely knowledgeable though. His dad did own some pretty nifty machines, so perhaps he intended to use one of those, which would make the synthesis dependent on having access to expensive equipment...



can i ask what you need chloroform for ?


----------



## 23536

does marijuana really threaten the profits of pharmaceutical giants, or is this just something that people like to say?  Have any professionals given an opinion on this (Wall Street market analysts or whatever)?

What specific products does it threaten, and which actions have been taken against marijuana?  By whom?


----------



## melange

well I have never really thought about it, but since you have asked , I would like to say yes, yes it does threaten them since these people are some of the most soulless scumbag greedy cocksuckers on the planet


----------



## Transform

I haven't heard of any "experts" weighing in, but if you think about it's soporific capabilities alone, then I think it would be able to at least compete with Z drugs, especially when you consider their side-effects. ("sleep"walking)
MJ is much less addictive than traditional pain management drugs, which I believe to be a pretty significant threat to the pharmaceutical companies. Even if it is only effective for mild to moderate pain, that's still a market which can be prescribed powerful opiates, especially in some less scrupulous clinics.
Then of course there the appetite stimulation, which has a smaller market but is probably still appreciable.


----------



## 23536

but you'd think that 75 years of prohibition would've resulted in at least some evidence, something a little more solid than speculation?



Transform said:


> MJ is much less addictive than traditional pain management drugs, which I believe to be a pretty significant threat to the pharmaceutical companies. Even if it is only effective for mild to moderate pain, that's still a market which can be prescribed powerful opiates, especially in some less scrupulous clinics.
> Then of course there the appetite stimulation, which has a smaller market but is probably still appreciable.



NSAIDs maybe sell better than opiates. If memory serves correct, celecoxib is very valuable to Lilly. My neighbor has M.S. and has a mounting stockpile of Celebrex, which he says has become useless to him ever since he got off probation and started smoking weed again. Actually he's piling the Celebrex right next to the Nexium because his stomach is no longer being torn up by daily ingestion of NSAIDs


----------



## hamhurricane

Yerg said:


> How do chemists discover drugs that are unrelated to a natural lead compound?



Generally they don't, at least in a single step. Drugs evolve gradually in a similar way to living organisms, hundreds and hundreds are created and some survive while others go extinct because they are toxic or have limited utility and, like living organisms, there may be serendipitous discoveries analogous to punctuated equilibrium but that is less common. Numerous platypus analogs had to be biosynthesized before the successful organism that is the platypus was created. The same could be said about something like pramiracetam, it's obviously a significant departure from piracetam but it was not discovered serendipitously, arduous screening of 50+ piracetam derivatives was required before that structure was arrived upon, so largely the process is repeated trial and error though which you often arrive at something unrelated to the lead compound...though that is changing a bit in recent years.


----------



## atara

--- said:


> has it been established that mdpv is mostly dopaminergic? at least two people agreed with that in the eadd mdpv thread, but many others have said there is far more adrenalin than dopamine in the mdpv experience, and that goes in line with my experience as well.



Trying to deduce the precise pharmacology of a compound from its subjective effects is highly error-prone. There are studies available on the action of MDPV; if there's something you'd like to read but can't PM me and I'll see what I can do.



> How do chemists discover drugs that are unrelated to a natural lead compound? How did, for instance, PCP or pethidine come to be created, and how was it deduced that they might be pharmacologically active? I'd just like to know how any drug is invented in a "revolutionary", rather than "evolutionary" way, without being based on SAR or rational design or anything.



http://en.wikipedia.org/wiki/Drug_discovery

Some I do know about: LSD was a total random accident. Pethidine is a simplification of the morphine rule.


----------



## vortex30

asecin said:


> can i ask what you need chloroform for ?



If you read back a page or two, nuke suggested it to someone for some purpose (I forget, lol), and someone asked if it was watched so I said that AFAIK it is probably watched, but also very easy to synthesize yourself.

As for my buddy's aspirations to synthesize it, I'm pretty sure that was just to waste a day together doing something 'educational' and being the crazy kid he was, he probably wanted to try knocking himself out with it, lol.


----------



## melange

asecin said:


> can i ask what you need chloroform for ?



it is a common solvent and reagent, is it not?


----------



## ebola?

It is.


----------



## ...

Can volatile radioactive material from Japan ride winds into China, or does the wind there never blow west? I'm not familiar with East Asian weather patterns but all the forecasts I see on NHK show continental wind blowing eastward.

I'm worried about the quality of the shit I buy online.


----------



## amanitadine

... said:


> Can volatile radioactive material from Japan ride winds into China, or does the wind there never blow west? I'm not familiar with East Asian weather patterns but all the forecasts I see on NHK show continental wind blowing eastward.
> 
> *I'm worried about the quality of the shit I buy online*.



good to see your heart is in the right place..8)


----------



## ...

amanitadine said:


> good to see your heart is in the right place..8)



How do you know I'm not buying antineoplastics for Honduran orphans?


----------



## amanitadine

good point


----------



## ebola?

Lol, not really.  
...
I would hazard a guess that chemo-toxicities (of varied sorts, from heavy metals to aromatic hydrocarbons) from manufactured goods from China outweigh the danger of radioactivity of goods from Japan.

(really, humans aren't particularly rational in choosing what to worry about)

ebola


----------



## Hyperthesis

... said:


> How do you know I'm not buying antineoplastics for Honduran orphans?


Because this is Bluelight and not the site of UNICEF...


----------



## Vader

What's the story with nasal/sublingual administration of water insoluble drugs? I often see people on here say "that's not soluble in water, you can't snort it", but people seem to have success taking benzos sublingually, and snorting freebase DMT. With the DMT, if it's active they can't just be swallowing it, so what gives?


----------



## asecin

vortex30 said:


> If you read back a page or two, nuke suggested it to someone for some purpose (I forget, lol), and someone asked if it was watched so I said that AFAIK it is probably watched, but also very easy to synthesize yourself.
> 
> As for my buddy's aspirations to synthesize it, I'm pretty sure that was just to waste a day together doing something 'educational' and being the crazy kid he was, he probably wanted to try knocking himself out with it, lol.




how much and how does it work to knock yourself out on it ? 
also im curious why its watched and hard to get if, as people here mentioned, its a common reagent and solvent ?


----------



## sekio

Couple of teaspoons, read Erowid for more info... it sure smells funny though.
It is indeed a common reagent and solvent but usually only sold to/found in labs.

I would hold off on inhaling huge amounts of chloroform though. The thing I don't like about it is that it turns into phosgene in your liver. I suspect chloral hydrate and others do too...


----------



## Captain.Heroin

Yerg said:


> What's the story with nasal/sublingual administration of water insoluble drugs? I often see people on here say "that's not soluble in water, you can't snort it", but people seem to have success taking benzos sublingually, and snorting freebase DMT. With the DMT, if it's active they can't just be swallowing it, so what gives?



You can snort drugs that are not very soluble in water, like triazolam, or DMT as you said.  

When people say "that's not water soluble - you can't snort it" they really don't know what they are talking about.


----------



## titstypedthis

does anyone have the half-life and melting points for 4-fluoroamphetamine?


----------



## Iodjini_dk

Yes


----------



## Lombergerh

Do I understand correctly that the 3-meo-pcp  it is a ether of pcp?
One guy told me that only alcohols can form esters (I don't quite understand what does it mean)


----------



## Captain.Heroin

Lombergerh said:


> Do I understand correctly that the 3-meo-pcp  it is a ether of pcp?
> One guy told me that only alcohols can form esters (I don't quite understand what does it mean)



3-meo-PCP is a member of the arylcyclohexylamine group of NMDA receptor antagonists.


----------



## Hyperthesis

3-MeO-PCP is an ether-derivative of PCP, that's correct. Please note that this is merely a formal way of naming it and doesn't have anything to do with the synthesis of 3-MeO-PCP. It is (partially) correct that only alcohols can form ethers (...which PCP is not!). Only _partially_, because you always need an alkylating agent (like a halogenalkan a lá methyliodide), which is not an alcohol itself. Anyway, then again isn't 3-MeO-PCP made from plain PCP.

The term "to form an ester" means by the way that a molecule with an alcohol-function, ie. a OH-group can be derivatized into an ether, ie. O-alkyl-moiety, with an appropriate reagent. For the latter exist numerous possibilities, but synthesis-talk is forbidden here, hence no further details from me.


----------



## Hyperthesis

forbiddenisdefruit said:


> I'm trying to do my own research but I can't find anything. What compounds are analogues of sugars?


Sugars _per se_ can indeed be turned into a drug, the most famous transformation being the fermentation of glucose into ethanol by yeast. Apart from this example it gets hard without unnecessarily much effort.
The point is that with enough patience, material and money (!) one can turn eg. glucose in almost anything that you want, but this would include several rather pointless chemical transformations and is hardly a viable approach. In other words: It's chemically possible, but absolute retarded, because a _much too expensive_ way.

Apart from that I can imagine a prodrug containing a sugar moiety, which gets cleaved off _in vivo_. That wouldn't render the sugar psychoactive on its own, but at least it would create a molecule containing a sugar-residue with psychoactive properties (...after one or two metabolisation steps). Not exactly what you asked for, but somehow related.

Analogues of sugars (in the narrower sense "carbohydrates", or in other words molecules fulfilling the general formula CxHyOx; x = 1 & y = 2 for glucose, 2 and 4 for sucrose respectively, etc.) are:
- sugar-alcohols, like mannose
- sugar-acids, ie. aldonic acids, ulosonic acids, uronic acids, aldaric acids (see Wiki for details)
- sugar-amines, like glucosamine​...and others.

None of them is psychoactive on its own, but some act as drugs, for example as laxative (eg. mannose).


----------



## ...

forbiddenisdefruit said:


> Can you convert a sugar molecule into a drug?



I was a bit enamored of pharmaceutical carbohydrates a year ago, because their structures are quite beautiful.  Here are examples:


Topiramate is directly synthesized from fructose (google the synthesis map):






 from 
	

	
	
		
		

		
		
	


	





Fondaparinux (an anticoagulant):







And of course heparin:


----------



## Hyperthesis

Ah see, I didn't ponder enough  All three abovementioned examples are indeed established drugs, although hardly psychoactive ones.


----------



## ...

Hyperthesis said:


> Ah see, I didn't ponder enough  All three abovementioned examples are indeed established drugs, although hardly psychoactive ones.



Good point.  The anticoagulants don't even target any receptors/tissue.  

Topiramate is psychoactive.  On a related note, even glucose is psychoactive (this is why epinephrine has a fleeting stimulatory effect).


----------



## Hyperthesis

Calling glucose psychoactive on its own would stretch the term "psychoactive" immensely, if you ask me. To what kind of activity in particular are you referring to?


----------



## ...

Hyperthesis said:


> Calling glucose psychoactive on its own would stretch the term "psychoactive" immensely, if you ask me. To what kind of activity in particular are you referring to?



Actually Hyperthesis I'd really appreciate your informed feedback on this.  A shot of from an Epi Pen has a transient stimulatory effect.  This is because epinephrine converts glycogen stores to glucose, thus increasing the rate of systemic and cerebral metabolism by elevating plasma glucose.  The reason this is interesting to me is that the cultural notion of an "adrenaline rush" is not all semantics and has actual biochemical underpinnings.

In simpler words, good feelings and euthymia (or a contented, upbeat mood) are always attainable, even without medication.  Is this a function of blood glucose?


----------



## Hyperthesis

Uhhhh, difficult, but nonetheless fascinating question.

First, I would not call increased glucose-levels resp. metabolic rates a psychoactive (re)action _per se_. I acknowledge that there are of course certain psychological effects felt, but I think that these are within the natural limits of what we just feel when blood pressure, heart rate etc. go up or down.
The stimulant effects from an epinephrine-pen shot derive IMO from epinephrine's own psychoactive action, respectively from its action on the heart and cardiovascular system. The time it takes to trigger glucose-release from glycogen-storages is certainly enough to get the drug into your brain as well.



> In simpler words, good feelings and euthymia (or a contented, upbeat mood) are always attainable, even without medication.  Is this a function of blood glucose?


If you have ever seen a patient with diabetes mellitus being heavily hypoglycemic than you know that blood glucose levels definitely influence the mood!


----------



## Amu

Is there any threshold human dose at which dextroamphetamine/methamphetamine neurotoxicity manifests itself? For example, significant at 20 mg but transient at 5 mg?


----------



## Hyperthesis

No. The range can't be defined precisely due to individual differences. This is just wishful thinking...


----------



## Amu

Hyperthesis said:


> No. The range can't be defined precisely due to individual differences. This is just wishful thinking...



Any estimates? How are we supposed to make informed decisions without any reliable data to guide us then? It seems we just have 50 articles that say different things.


----------



## nuke

In rats it doesn't take much, I think 1mg/kg

http://www.ncbi.nlm.nih.gov/pubmed/12452543

I think bottom line is not to do meth if you don't want neurotoxicity.  Amphetamine is a reasonably safe alternative in that regard.


----------



## ebola?

When examining the activity of monoamine releasers, we examine efficacy rather than binding affinity, as most of their activity is from reverse transport rather than prohibition of reuptake.  However, does efficacy in vast excess of what we'd otherwise expect (that is, as we'd expect from a mere reuptake inhibitor with the same binding affinity) directly imply activity as a releaser?  Or would we need additional confirmation, independently demonstrating affinity for transporters as substrates?

ebola


----------



## Amu

nuke said:


> In rats it doesn't take much, I think 1mg/kg
> 
> http://www.ncbi.nlm.nih.gov/pubmed/12452543
> 
> I think bottom line is not to do meth if you don't want neurotoxicity.  Amphetamine is a reasonably safe alternative in that regard.



It would be great if there was a section on neurotoxicity in the Bluelight Neuropharmacology Text, discussing the relative neurotoxicity of methamphetamine, amphetamine, MDMA, Methylphenidate, Cocaine, and other recreational/psychiatric drugs besides stimulants.

This is against intuition so to speak, but it's interesting "Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286/


----------



## ebola?

It's not that counter-intuitive: methylphenidate appears neuroprotective insofar as it limits methamphetamine's efficacy (and indeed, they examined proposed mechanisms at DAT and VMAT2).  Less intuitive, however, are the proposed effects on genetic expression related to vesicular formation.  It's here that I think my knowledge incomplete.

ebola


----------



## ebola?

It's not that counter-intuitive: methylphenidate appears neuroprotective insofar as it limits methamphetamine's efficacy (and indeed, they examined proposed mechanisms at DAT and VMAT2).  Less intuitive, however, are the proposed effects on genetic expression related to vesicular formation.  It's here that I think my knowledge incomplete.

ebola


----------



## drzoidbergphd

could use some ADD knowledge/input in this thread for those of you who haven't seen it.

http://www.bluelight.ru/vb/showthread.php?t=565045


----------



## Munroe

Have any other "dragon-fly" compounds been investigate? Chloro, fluro, ethyl etc?
If not, whats the reason for this? 

also, has "bromo-dfly"s phenthylamine analogue been looked into? Aside from 2C-B-FLY.


----------



## jaguraguguru

Hyperthesis, epinephrine doesn't cross the blood-brain barrier, so it is not directly psychoactive. It has powerful effects on the peripheral/autonomic nervous sytems, which can influence mental state secondarily. Also, you're right about glucose influencing moods, but germanely to this discussion, it only influences mood below the normal/necessarylevel, but not above it. Hyperglycemia is not acutely psychoactive and is not a performance enhancer to any great extent.

Neurotoxicity of amphetamine, methamphetamine, MDMA, and MDA at anything less than heroic doses has not been shown in humans to the best of my knowledge. It has been shown in rodent models for sure for many of these, but also usually with extreme doses, multiple acute doses, or chronically.


----------



## ebola?

> Neurotoxicity of amphetamine, methamphetamine, MDMA, and MDA at anything less than heroic doses has not been shown in humans to the best of my knowledge.



Since it's extremely difficult to simulate chronic, low-level dosing, it's extremely difficult to demonstrate neurotoxicity directly generalizable to humans.  It's for this reason that it was difficult to establish amphetamine as relatively benign in low doses and methamphetamine neurotoxic at commonly encountered recreational doses (and this is why the conclusions about entactogens remains unclear).

ebola

edit: upon giving your post a more thorough reading, you appear to know all this.


----------



## ebola?

nuke said:
			
		

> In rats it doesn't take much, I think 1mg/kg
> 
> http://www.ncbi.nlm.nih.gov/pubmed/12452543



With a cursory look, 1 mg / kg was a dose used to measure long-term behavioral consequences from a prior neurotoxic dose (5 mg / kg, 3 times, separated by 3 hours).  This study doesn't seem to be the best from which to generalize neurotoxicity (particularly given their operationalization of neurotoxicity).  Nonetheless, people do get that tweaked in a sitting sometimes (you crazy motherfuckers ).

ebola


----------



## nuke

Ah, thanks for going over the methods for me then.  Usually the dose for neurotoxicity is 5mg/kg-10mg/kg it seems like


----------



## Amu

nuke said:


> Ah, thanks for going over the methods for me then.  Usually the dose for neurotoxicity is 5mg/kg-10mg/kg it seems like



The HED dose is about 6.2 times less than rat doses according to the FDA, so between 60-120mg of amphetamine for a 70kg person.

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078932.pdf


----------



## ebola?

Should we expect the threshold for neurotoxicity to scale with the threshold for efficacy?  In lieu of more specific indicators, I guess so.  Now, the question is, is this the threshold for neurotoxicity to be set at clear physiological damage in an individual, clear enduring behavioral deficits in an individual, or statistical trends discernible in populations exposed to neurotoxic conditions?

ebola


----------



## Amu

ebola? said:


> Should we expect the threshold for neurotoxicity to scale with the threshold for efficacy?  In lieu of more specific indicators, I guess so.



Unfortunately, the answer could be no.



			
				Baggott and Mendelson said:
			
		

> In general, smaller species excrete drugs more quickly and form metabolites in greater amounts than larger species. This is due to many factors including the proportionally larger livers and kidneys and faster blood circulation times in smaller mammals (Lin 1998; Mordenti,1989). As a result of such factors, the time it takes to lower the plasma levels of MDMA by half is about 1.5 hours in a rat (Cho, 1990) and about 8 hours in a human (Mas, 1999). This suggests that small species may require higher doses to achieve drug exposures comparable to those seen in larger species.



So 5 mg/kg in rats / 6.2 = 0.8 mg/kg for surface area, then taking blood circulation times into account 0.8 mg/kg / (8/1.5) = 0.15 mg/kg for humans, that's only 10.5 mg in 70 kg person. This estimate might be low considering there is overlap between the body surface area conversion factor and the blood circulation time conversion factor.

Also, it is very possible that dextroamphetamine is more harmful to dopaminergic neurons than methamphetamine is, as it activates these neurons in more parts of the brain. A friend of mine ran into a toxicity study that found dextroamphetamine caused dopamine deficits in three regions of the brain compared to methamphetamine causing deficits in one region.


----------



## Jellybelly92

What is the best alternative to diethylamine?


----------



## Vader

For what purpose? Obviously not drug synthesis, that's against the rules.


----------



## Munroe

Munroe said:


> Have any other "dragon-fly" compounds been investigate? Chloro, fluro, ethyl etc?
> If not, whats the reason for this?
> 
> also, has "dfly"s phenthylamine analogues been looked into? Aside from 2C-B-FLY.



Quoted cause I managed to post at an inopportune moment


----------



## ebola?

> What is the best alternative to diethylamine?



flatus: like diethylamine, it is colorless with a pungent odor. ;P

ebola


----------



## Vader

^Most highbrow fart joke I've read today.


----------



## Klonopin King

which receptors are responsible for the release of chemicals such as serotonin dopamine, norepinephrine, and so on if so inclined, thank you in advance!

-KK

Also one can exclude the 5ht receptors as i have found that they release a broad list of chemicals, and furthermore if this is a task in it's own to name the receptors because alot of receptors are responsible for these chemical releases not just one i apologize but for example what receptor is responsible for dopaminergic activity while on opiates, thanks.


----------



## psood0nym

I just want to confirm that what I think will happen will happen before I do it:

If one slowly adds a solution of hydrochloric acid (pool cleaner) to aMT freebase until all the aMT is dissolved, then evaporates off the water, what is left is aMT HCl, correct? There's no excess HCl or need to calculate moles because excess HCl evaporates into the atmosphere, right?


----------



## Vader

Yep.


----------



## psood0nym

^Thanks. Easy peasy.


----------



## Amu

Which drugs cause a peripheral blockade of adrenoreceptors?


----------



## acetylcholine

I assume you are interested in attenuating potentially severe a1-mediated peripheral vasoconstriction and resulting tissue death caused by substituted cathinones and the like. If that's not the case, then my apologies. Anyway, I suppose any a1 blocker will due, say prazosin- I'm not sure about BBB issues but if you are on a stimulant, a little central a1 blockade shouldn't be a big deal.

HOWEVER, I remember reading that using a1 blockers for this purpose is a bad idea because of the risk of tachycardia.


----------



## Amu

acetylcholine said:


> I assume you are interested in attenuating potentially severe a1-mediated peripheral vasoconstriction and resulting tissue death caused by substituted cathinones and the like. If that's not the case, then my apologies. Anyway, I suppose any a1 blocker will due, say prazosin- I'm not sure about BBB issues but if you are on a stimulant, a little central a1 blockade shouldn't be a big deal.
> 
> HOWEVER, I remember reading that using a1 blockers for this purpose is a bad idea because of the risk of tachycardia.



Thanks for the response. Actually I was asking in order to discover how to block cocaine/amphetamine-induced anxiety/agitation. Beta blockers don't work, and I doubt Benzos would be a good choice. I'm currently trying to see if a calcium channel blocker can help with Cannabis-induced anxiety and panic attacks, and I've read they can help the same problem encountered with stimulants. There has to be a direct mechanism that causes these issues with stimulants that can be taken care of without affecting the high/euphoria or causing further problems. Tachycardia could be an issue with prazosin.


----------



## acetylcholine

Interesting stuff Amu. Have you seen papers suggesting this and can you link?

Are the Ca channel agents you are considering anticonvulsants like, say, gabapentin?


----------



## pharmakos

just based on the way that pregabalin felt in me, i'd say that it very likely would block amphetamine anxiety/jitters.


----------



## Amu

acetylcholine said:


> Interesting stuff Amu. Have you seen papers suggesting this and can you link?
> 
> Are the Ca channel agents you are considering anticonvulsants like, say, gabapentin?



http://www.ncbi.nlm.nih.gov/pubmed/18195452
http://www.ncbi.nlm.nih.gov/pubmed/11165225
http://www.ncbi.nlm.nih.gov/pubmed/9299207

http://www.ncbi.nlm.nih.gov/pubmed/2076753

Calcium channel blockers such as Verapamil can block amphetamine induced-anxiety/psychosis/aggression without affecting the primary dopamine release.

Interesting you mention Gabapentin, I haven't read any studies directly on the effects of it on amphetamine's effects, but I'm sure it would have certain positive effects.


----------



## acetylcholine

Amu said:


> http://www.ncbi.nlm.nih.gov/pubmed/18195452
> http://www.ncbi.nlm.nih.gov/pubmed/11165225
> http://www.ncbi.nlm.nih.gov/pubmed/9299207
> 
> http://www.ncbi.nlm.nih.gov/pubmed/2076753
> 
> Calcium channel blockers such as Verapamil can block amphetamine induced-anxiety/psychosis/aggression without affecting the primary dopamine release.
> 
> Interesting you mention Gabapentin, I haven't read any studies directly on the effects of it on amphetamine's effects, but I'm sure it would have certain positive effects.



Thanks for the links!


----------



## pharmakos

what about this molecule?  you could think of it as alpha-desmethyl-6-APB (edit/correction: it'd be 6-APDB the way i have it drawn, and it's not just alpha-desmethyl but also has an added oxygen at the 2-position...), but i like to think of it as 2C-E with the 4-ethyl bonded to the 5-oxygen.  should there be a double bond there instead of a single?  IDK i haven't even taken an O-Chem course.

anyway, what do you guys think of molecules like this in general?  the sort of half-way point between the 2C family and the MDA family...  could the 2-position oxygen make it so that there is empathogen activity even without the alpha-methyl?  perhaps it's active as a psychedlic similar to 2C-E, 2C-D, MDA, or MMDA-2?






just to reiterate, in case there's any vendors out there looking at this -- i am a dumb ass when it comes to O-Chem, and this stuff very well could be a neurotoxin for all i know.

edit -- surely someone has to have dreamed up or even created this stuff somewhere at some point in time!  am i correct in naming it 5-Methoxy-6-(2-Aminoethyl)-2,3-dihydrobenzofuran?  i think 5-Methoxy-6-(2-Aminoethyl)benzofuran is the name of what i MEANT to draw.


----------



## vecktor

^ both drawings are the same molecule (I assume you are aware of that)

for hallucinogenic activity the SAR that deals with these molecules is that determined by nichols et al with the dragonflies and hemidragonflies, however the 2,4,5 hemifly excuse the numbering with the dihydrofuran ring at the 4,5 positions is not a very active 5ht2a agonist. the simple rule of thumb is you can only bend back the methoxy into a dihydrofuran into positions that do not involve the 4 position, it isn't quite as simple as that but that is the essence. it has to do with what direction the oxygen lone pairs point. if the furan is replaced with a methylenedioxy ring then there is some activity, but then perhaps the molecule is more like a 3,4,5 phenthylamine in the way it binds and they usually have slightly different binding to 2,4,5 phenthylamines at 5ht2a.

as to empathogenic activity who knows? instinct says it will be thoroughly inactive it is probably a good enzyme substrate and so gets chewed, the related methylenedioxy compound has not been properly tasted to my knowledge, shulgin briefly discusses it in pihkal.

from pihkal #133 MMDA-2


> The phenethylamine analog of MMDA-2 has been prepared by the condensation of the above benzaldehyde with nitromethane (in acetic acid with ammonium acetate catalyst, giving an equal weight of the nitrostyrene as deep orange crystals with a mp of 166-167 °C from ethyl acetate) followed by lithium aluminum hydride reduction (in ether). The product, 2-methoxy-4,5-methylenedioxyphenethylamine hydrochloride (2C-2) melted at 218-219 °C. There were no effects observed at up to 2.6 milligrams, but no higher trials were made.



I wouldn't go near this or the  methylenedioxy compound  because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.


----------



## Vader

How come TMPEA (2,4,5-trimethoxyphenethylamine) isn't active? TMA-2 is more potent than TMA, 2C-T is active, the 2,4,5 pattern is a winner in general, I assumed that this one would be a gem but Shulgin says no activity at 300 mg. Any idea why?


----------



## pharmakos

vecktor said:


> ^ both drawings are the same molecule (I assume you are aware of that)
> 
> for hallucinogenic activity the SAR that deals with these molecules is that determined by nichols et al with the dragonflies and hemidragonflies, however the 2,4,5 hemifly excuse the numbering with the dihydrofuran ring at the 4,5 positions is not a very active 5ht2a agonist. the simple rule of thumb is you can only bend back the methoxy into a dihydrofuran into positions that do not involve the 4 position, it isn't quite as simple as that but that is the essence. it has to do with what direction the oxygen lone pairs point. if the furan is replaced with a methylenedioxy ring then there is some activity, but then perhaps the molecule is more like a 3,4,5 phenthylamine in the way it binds and they usually have slightly different binding to 2,4,5 phenthylamines at 5ht2a.
> 
> as to empathogenic activity who knows? instinct says it will be thoroughly inactive it is probably a good enzyme substrate and so gets chewed, the related methylenedioxy compound has not been properly tasted to my knowledge, shulgin briefly discusses it in pihkal.
> 
> from pihkal #133 MMDA-2
> 
> 
> I wouldn't go near this or the  methylenedioxy compound  because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.



thanks for the response, you've given me a lot to think about and research.

p.s. i was aware that the two drawings were of the same molecule.  i just figured seeing both perspectives would help creative thinking.


----------



## sackynut

i hear 2methylmdma is one of the more potent and active analogs, this true? shulgin hints at it, and no one on the net seems to want to bring it up...


----------



## debaser

http://isomerdesign.com/Cdsa/poster.php

Don't know if this link has already been posted or not, but I figured it could be of valuable interest for all the bluelighters.


----------



## pharmakos

randomly thought this one up while the site was down... i can't find anything about it anywhere, but i figure Nichols must have at least thought of it...

2,5-dimethoxy-4-hexafluoroisopropylphenethylamine, 2C-HFIP

so american of me (2C-TFM is awesome with 3 fluoros out there, lets get twice as many on that 4-position! XD), but still, it made me drool a little bit when i thought it up lol 

any thoughts on this stuff, or on why nichols hasn't made it yet?  i've also got a feeling that there's a pretty obvious answer to that question =p

oh, and i don't feel too bad about posting this chemical wankery, because i'm pretty sure that the chemistry involved in making this stuff would be prohibitively expensive enough that this will not reach the "research chemical" masses...


----------



## skillet

You can get 7 fluorines on an isopropyl group  Though I'd probably rather the n-heptafluoropropyl version.



vecktor said:


> I wouldn't go near this or the  methylenedioxy compound  because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.



That's a good point, and I guess 6-OH-alpha-Me-dopamine is just as neurotoxic? Do you think this is a bigger issue with MMDA-2 than TMA-2, ie. is demethylenation (think it's a word!) faster than demethylation? Not that it really matters, MMDA-2's not very nice anyway; 'some not-too-pleasant jangly effects,' as the first entries in pihkal says!


----------



## MasterOfDeception

*SSRIs *work by *inhibiting *the *reuptake *mechanism of a neuron, and that results in greater *serotonin **activity *in the *serotoninergic *receptors. 

A *serotine antagonist* does pretty much the opposite, it *blocks *serotonin activity in the receptors.

So, since *SSRIs *are supposed to be *antidepressants*, serotonin antagonists can cause depression ? I am asking cuz most/all 2nd generation antipsychotics are serotonin antagonists, amongst others.


----------



## freemind

Hi.

What about N,N-dimethylphenylethylamine?





Chemistry? Toxicity?
Has anyone ever tried it?

And derivatives, like N,N-dimethyl-alfa-methylphenylethylamine?

I was thinking about AMT, the "tryptamine version" of amphetamine, and wondered, why not a "phenylethylamine version" of DMT?


----------



## ebola?

> So, since SSRIs are supposed to be antidepressants, serotonin antagonists can cause depression ?



Apparently not.  It seems that SSRIs work (insofar as they do--they are only marginally effective) via some sort of downstream effect, not generalized increase in serotonergic signalling.

ebola


----------



## MasterOfDeception

ebola? said:


> Apparently not.  It seems that SSRIs work (insofar as they do--they are only marginally effective) via some sort of downstream effect, *not generalized increase in serotonergic signalling*.
> 
> ebola



Ok the bold part partly answers my question.
However I read in wiki that SSREs (reuptake Enhancers) work as much as the SSRIs (reuptake inhibitors). How is that possible? 

And what exactly is the *downstream effect *? That would help.


----------



## Wizzle

Atypical antipsychotics usually antagonize serotonin 2A and 2C receptors, which increases signalling to all other serotonin receptors, theoretically having an antidepressant (because of increased activating of s1A receptor/anti-anxiety(2A antagonism)/antipsychotic (2C antagonism) effect.


----------



## MasterOfDeception

Wizzle said:


> Atypical antipsychotics usually antagonize serotonin 2A and 2C receptors, which increases signalling to all other serotonin receptors, theoretically having an antidepressant (because of increased activating of s1A receptor/anti-anxiety(2A antagonism)/antipsychotic (2C antagonism) effect.



Thnx for the reply. However why antagonizing 2A and 2C results in increased activity to other serotonin receptors? It might seem kind of obvious but I would like to see it explained more analytically. Serotonin neurotransmitters can't use 2A and 2C so they use the remaining receptors? The exact same serotonin neurotransmitter can bind to any serotonin receptor?


----------



## freemind

Are the active principles of nutmeg, myristicin and elemicin, soluble in alcohol, water, acetone, or in any other solvent?


----------



## nuke

freemind said:


> Are the active principles of nutmeg, myristicin and elemicin, soluble in alcohol, water, acetone, or in any other solvent?



Solubility looks like this:
Diethyl ether = Hexane > Acetone > Ethanol > Water


----------



## ebola?

> However I read in wiki that SSREs (reuptake Enhancers) work as much as the SSRIs (reuptake inhibitors). How is that possible?



Tianeptine's modest efficacy as an SSRE might not explain it's anti-depressant action (though coadministration with SSRIs reduces drastically T's effects on long-term potentiation).  T also acts at AMPA and NMDA sites and causes downstream increase in intercellular monoamines.

ebola


----------



## Wizzle

MasterOfDeception said:


> Thnx for the reply. However why antagonizing 2A and 2C results in increased activity to other serotonin receptors? It might seem kind of obvious but I would like to see it explained more analytically. Serotonin neurotransmitters can't use 2A and 2C so they use the remaining receptors? The exact same serotonin neurotransmitter can bind to any serotonin receptor?



That's exactly how it is.


----------



## freemind

nuke said:


> Solubility looks like this:
> Diethyl ether = Hexane > Acetone > Ethanol > Water


Thanks, nuke.


----------



## acetylcholine

MasterOfDeception said:


> *SSRIs *work by *inhibiting *the *reuptake *mechanism of a neuron, and that results in greater *serotonin **activity *in the *serotoninergic *receptors.
> 
> A *serotine antagonist* does pretty much the opposite, it *blocks *serotonin activity in the receptors.
> 
> So, since *SSRIs *are supposed to be *antidepressants*, serotonin antagonists can cause depression ? I am asking cuz most/all 2nd generation antipsychotics are serotonin antagonists, amongst others.



Some theories on SSRI efficacy regard postsynaptic 5-HT2 and presynaptic 5-HT1 family receptor desensitization and down-regulation due to increased synaptic 5-HT as the actual mechanism. The long term consequence of an SSRI or 5-HT2 antagonist would thus be similar.


----------



## Respectable junkie

hi all  I wanted to take some promethazine to potentate some DHC but i have had 75mg of amytriptyline an hour or 2 ago and i read somewhere on the net there are 'a moderate interaction' between amytriptyline and promethazine. Can someone elaborate for me please, does this mean steer clear or preceed with caution? has any1else had a bad reaction mixing the two?


----------



## Enkidu

Do phenazone or its derivatives have any abuse potential?

Torizo Takahashi has some interesting papers.


----------



## 23536

How is thalidomide a sedative?  What does it do up there?


----------



## sekio

I was under the impression that thalidomide was comparable to the barbiturates or glutethimide.


----------



## Enkidu

Enkidu said:


> Do phenazone or its derivatives have any abuse potential?



You're all worthless


----------



## Vader

^That's not the kind of endearing attitude that makes other posters want to help you. Don't be a dick.


----------



## ebola?

At first, I thought that he was calling himself worthless. 

ebola


----------



## snt8j4

Hi,

I was thinking about mephedrone and...How fast will be converted to 4-methylephedrine?  Is it possible that this metabolite plays an important role in its effect (stimulant part)? 
I mean

Meth(strong stimulant) -> MDMA(milder stimulant)
Amphetamine(medium stimulant) -> 6-APB(milder psychedelic like stimulant)

Methcathinone(mild stimulant / entactogen?)-> 4-MMC(very strong and potent entactogenic drug and stimulant)

and even more important

Amphetamine(medium stimulant)->4-MA(potent serotonine releasing agent, not really stimulant)



4-N-Methyl is a magical group on methcathinone, or what? Why is meph so potent and fast?


----------



## Enkidu

Mephedrone releases both serotonin and dopamine in large amounts. A large release of serotonin has a 'muting' effect on the stimulant effects dopamine releasers.


----------



## Enkidu

If you speak japanese, please PM me. This "translation job" is mostly reading.


----------



## Epsilon Alpha

Does anyone know if there are any major differences between catecholamine catabolism in the PFC vs the limbic system in regards to proportions broken down by COMT vs MAO?

I've been searching around but can't find anything definitive for humans.


----------



## nuke

What is it like in other species?


----------



## Epsilon Alpha

nuke said:


> What is it like in other species?



I don't have the studies saved on this computer, but it looks really inconsistent in SD rats but COMT generally breaks down 50-60% of DA in general.


----------



## knock

*Mechanism of potentiation of methoxetamine by methiopropamine*

Several BLers have reported that the stimulant RC methiopropamine potentiates the dissociative methoxetamine. I myself have had an experience where a dose of methoxetamine which is well within my regular range, about 40mg, combined with an unknown but not huge quantity (perhaps 70mg) of methiopropamine resulted in me behaving erratically (trying to pee against a wall) and having to be put to bed several times - and I have no memory of these events.

Alcohol and o-desmethyltramadol were also involved, but they have been before without any such issue, the methiopropamine was the only novel factor.

Is the potentiation mechanism understood, and if so what is it? Is it something likely to be encountered with other stimulants and dissociatives?

I'm intrigued because I haven't previously noticed such a powerful effect of combinations in my drug taking experience, other than cannabis potentiating methoxetamine, and I'd be interested to understand that too (no amnesia/irrational behaviour there though, just extreme psychedelia and stimulation).

Thanks for any replies in advance.


----------



## ebola?

Many people have had experiences where stimulants potentiate dissociatives in general.  The precise mechanism is unknown.  However, alcohol and tramadol should also exert such potentiation, exerting minor NMDA antagonism.

ebola


----------



## jemery619

*research chems*

trusted sites???


----------



## nuke

bluelight.ru


----------



## nuke

> Br J Dermatol. 2011 Jun 28. doi: 10.1111/j.1365-2133.2011.10490.x.
> Serotonin induces melanogenesis via serotonin receptor 2A.
> Lee HJ, Park MK, Kim SY, Park Choo HY, Lee AY, Lee CH.
> 
> College of pharmacy, Dongguk University, Seoul 100-715, Korea Graduate School of East-West Medical Science, Kyung Hee University Global Campus, #1 Seocheon-dong, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea College of Pharmacy & Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea Department of dermatology, College of medicine, Dongguk University, Ilsan Hospital, Goyang, Korea.
> 
> Background:  The serotonin levels were increased by light exposure but the role and mechanism of serotonin in the pigmentation of skin cells are unclear. Objectives:  To clarify the effect of serotonin on melanogenesis and to determine the serotonin receptor subtype involved. Methods:  B16F10, SK-MEL-2 and Melan-a cells were cultured DMEM with low FBS. Three cell lines were treated with various concentration of serotonin (5-HT), 5-HT receptor agonists, and antagonists. The involvement of the 5-HT receptor 2A (5-HTR2A) was examined by gene silencing and 5-HTR2A antagonists. Results:  5-HT and the 5-HTR2A agonist, DOI increased the melanogenesis in three cell lines. These increased events were suppressed by 5-HTR2A antagonists or gene silencing of the 5-HTR2A gene. Conclusions:  The serotonin receptor 5-HTR2A is involved in melanogenesis. These findings highlight the role of serotonin and suggest new ways of controlling melanogenesis.



So not only will DOI make you trip balls, it'll help you get that California tan you always wanted too!


----------



## ebola?

hahahah.


----------



## ToxicFerret

Can someone explain to me something about the structures of the 2C-X drugs? Basically, without getting into any synth details, I would like to know why when a halogen is bonded to 2C-H it ens up in the 4 position instead of the 1 or the 3. My hypothesis would be that it has to do with the electrostatic potential at that location (para, or 4 position) on the phenyl. The other available positions are closer to the mass of electrons that are part of the ethylamine carbon chain. Anything close to the actual answer or am I talking BS?


----------



## 23536

steric hindrance to electrophilic substitution at other positions on the ring?


----------



## sekio

6' bromination also happens in e.g. illicit production of 2cb if the conditions are not controlled, I thought.


----------



## ToxicFerret

Cool so it's really that there are a couple of different reasons all working in concert to make the 4-position the most friendly to halogen substitutions.


----------



## Iodjini_dk

Both the methoxy groups and the aliphatic chain are ortho/para directing with regards to aromatic susbstitution. If bromination was to occur at the 3' position it would be meta to two ortho/para directing groups and therefore not as favorable as the 4' position. As seiko mentions bromination could also occur at the 6' position as it would be ortho to two groups and meta to one as the 4' position. However the 6' position is more sterically hindered due to the aliphatic chain. Also the amine is probably protonated under the reaction conditions. This destabilizes the partly charged transistion state at the 6' position.  Its mostly about sterics and electronics


----------



## yoyoman

EDIT:  Wikipedia was wrong saying dexamp is (R) so i changed it.  Teaches me not to rely on wikipedia as much.
Spent a while trying to figure it out, ends up its just that somebody put the wrong IUPAC name for dextroamphetamine .  So a lot of this below i get now.


I have a question regarding ChemBioDraw Ultra.





i forgot how to imbed an image apparently so here's the link:
http://anony.ws/di-1Z9H.gif

I'm puzzled with (S) and (R), dextro and levo.  Why when i simply select the molecule, and invert it vertically does the R change to an S or visa versa?  Do I have a corrupt copy of ChemOffice?

I was trying to make a correct image of the dextro versions of N-hydroxy-amphetamine or N-hydroxy-N-ethylamphetamine etc.  Also the wedged bond and hashed wedged bond is confusing.  Sometimes it will put the chiral carbon towards the amine if i type something into "convert name to structure".  I don't remember previous versions of chemdraw doing things like this..  

Is (R)-amphetamine and (R)-methamphetamine both the dextro versions? Google turns up different results, some saying d-meth is (S) etc.  Apparently both are (S).  Never mind..ehh.


----------



## pharmakos

when you flip it two-dimensionally you are in effect creating the original molecule's mirror image (its optical isomer if my terminology is correct... never taken orgo).  if you wanted the oxygen to point downwards without changing which optical isomer you are looking at you would need to rotate the molecule so that the phenyl is on the right rather than flipping it.

look at the original and the flipped molecule... there's no way you could rotate them in 3D space so that they overlap, right?  therefore they are optical isomers.


----------



## yoyoman

Wow, thanks for that!  I'll fool around with it.

But this version sucks.. The useful tool "Convert name to structure" its like they went backwards, more like a downgrade. I used to be able to type in all sorts of stuff like d-amphetamine, levoamphetamine, now it doesn't understand that.  I have to be very specific.  Gonna try this chemsketch its free.


----------



## mukaki

I have a three-part question.

1. I am taking 200 mg of amisupride every morning. At this dosage it "preferentially block inhibitory pre-synaptic autoreceptors". What does that mean?

2. What will the effect of that dosage of amisulprider be with regards to various stimulants?

3. Somehow I seem to get more euphoria when I take amisulpride. Is that "right"? Or is it just placebo?


----------



## lab slave

Hi guys,

Was hoping to get chemistry info about the pill-test kits. My understanding is limited. So (in the marquis) sulphuric acid acts as a catalyst and formaldehyde reacts with the compound to produce new compounds. These new compounds have colours? Can someone go into some detail?

Can someone think of an improved test kit? Would it be possible (theoretically) produce a test kit (or series of kits) that was able to make finer distinctions between compounds?


----------



## skillet

mukaki said:


> I have a three-part question.
> 
> 1. I am taking 200 mg of amisupride every morning. At this dosage it "preferentially block inhibitory pre-synaptic autoreceptors". What does that mean?
> 
> 2. What will the effect of that dosage of amisulprider be with regards to various stimulants?
> 
> 3. Somehow I seem to get more euphoria when I take amisulpride. Is that "right"? Or is it just placebo?



1. The axon of the pre-synaptic neuron stores, produces(?) and releases neurotransmitters into the synaptic cleft where they bind to receptors on the post-synaptic neuron, transmitting a signal. Autoreceptors are located on the pre-synaptic neuron and bind the same neurotransmitter, but the effect is generally to reduce the amount of neurotransmitter produced/released by the neuron, so they provide negative-feedback to regulate neurotransmitter release. Blocking dopamine autoreceptors will increase dopamine release and, therefore, dopaminergic neurotransmission.

2. I guess it would potentiate the dopaminergic component of stimulants.

3. That's the effect I'd expect, though I tried 100mg amisulpride and maybe 5mg aripiprazole and noticed no effect. Were you told it should have that effect when you started taking it?

I have a related question, a doctor prescribed low dose (5mg) aripiprazole to try to counteract hyperprolactinemia caused by risperidone (8mg I think, amisulpride initially caused the problem, was switched to risperidone with no improvement.) Don't know if it's working yet, but is there any reason to think this would be any different to simply reducing the dose of risperidone slightly? I'd expect the overall effect to be the same, a slight increase in dopaminergic transmission, unless there's maybe selectivity for different brain areas between the two drugs?



lab slave said:


> Hi guys,
> 
> Was hoping to get chemistry info about the pill-test kits. My understanding is limited. So (in the marquis) sulphuric acid acts as a catalyst and formaldehyde reacts with the compound to produce new compounds. These new compounds have colours? Can someone go into some detail?
> 
> Can someone think of an improved test kit? Would it be possible (theoretically) produce a test kit (or series of kits) that was able to make finer distinctions between compounds?



There are several reagent tests you can use, see the wiki page.


----------



## lab slave

There are several reagent tests yes, and using them in combination helps narrow the results, but there is only so narrow they can go. I'm mostly interested in understanding the reaction(s).


----------



## mukaki

skillet said:


> 1. The axon of the pre-synaptic neuron stores, produces(?) and releases neurotransmitters into the synaptic cleft where they bind to receptors on the post-synaptic neuron, transmitting a signal. Autoreceptors are located on the pre-synaptic neuron and bind the same neurotransmitter, but the effect is generally to reduce the amount of neurotransmitter produced/released by the neuron, so they provide negative-feedback to regulate neurotransmitter release. Blocking dopamine autoreceptors will increase dopamine release and, therefore, dopaminergic neurotransmission.
> 
> 2. I guess it would potentiate the dopaminergic component of stimulants.
> 
> 3. That's the effect I'd expect, though I tried 100mg amisulpride and maybe 5mg aripiprazole and noticed no effect. Were you told it should have that effect when you started taking it?


Thank you for the quick and precise answer. The stimulants I take are not prescribed, and my psychiatrist did not say anything about stimulants. I don't think she knows that's how amisulpride works....


----------



## atara

lab slave said:


> Hi guys,
> 
> Was hoping to get chemistry info about the pill-test kits. My understanding is limited. So (in the marquis) sulphuric acid acts as a catalyst and formaldehyde reacts with the compound to produce new compounds. These new compounds have colours? Can someone go into some detail?
> 
> Can someone think of an improved test kit? Would it be possible (theoretically) produce a test kit (or series of kits) that was able to make finer distinctions between compounds?



Thin-layer chromatography would be the way to go. I doubt you'd get people signing up to buy a TLC kit, it's cheap but a bit complicated for the typical raver.

DanceSafe sells multiple reagent tests which is the best you'll likely do.


----------



## Iodjini_dk

Well, you also need reference compounds of relatively high purity for a TLC analysis to work properly. I agree that TLC analysis would be a bit too complicated for the average raver.


----------



## pharmakos

Iodjini_dk said:


> Well, you also need reference compounds of relatively high purity for a TLC analysis to work properly. I agree that TLC analysis would be a bit too complicated for the average raver.



with enough standardization i don't think the end user would need high purity reference compounds


----------



## skillet

Maybe not high purity, but I'd have thought you need some sort of reference. I guess Rf depends somewhat on moisture content of the silica (or whatever), particle size, maybe temperature, solvent saturation of the chamber atmosphere, and maybe some other stuff?


----------



## Iodjini_dk

^^Thats why one cannot always rely on Rf values alone. A stated Rf value in a given solvent only provides an interval of some sort. It can vary as much as 0.3 IME. But maybe a device could be made that controls some of these factors as solvent saturation, chamber atmosphere etc. Sounds a bit expensive though 
The reason for high purity reference compounds is that even minor impurities can give rise to big spots in a TLC analysis. I dont know for sure but I could imagine that the average street drugs give rise to numerous spots in a TLC analysis as they are rarely purified.


----------



## A Lucid Pet

I guess this would probably go here before it got it's own thread. Kinda caught between Cannabis discussion and ADD here. 

Well I was making some canna-butter by boiling a little over a pound of butter, water and plant material in a pot for about an hour. I was going to strain this mixture and let it cool so the butter would coagulate and separate from the water. At the last second I decided to use a pitcher to pour the mixture into the filter and washed it out really quick with palmolive dish soap. Apparently I didn't rinse it out as well as I had thought. 

Upon pouring the mixture into the pitcher I noticed the soap bubbles but didn't really think much of it. When I make butter I usually put ice in the solution to hasten the cooling of the butter-water solution. Right away I could see that the remaining soap was not going to let the butter coagulate properly because of it's ant-grease properties (whatever those may be lol). 
I tried to skim the butter off of the top of this solution and put it over ice in a bowl and put it in the freezer hoping I could just separate the ice from the frozen butter easily and then make some soapy cookies. The ice and the butter did not separate easily and so I had to soften the butter to get the ice out. My concern is/was that the soapy water had mixed with the butter enough so that if I tried to defrost it it would defrost into a sludge which is butter being broken down. My fears were confirmed. After sitting in the fridge, not the freezer, for about a day the ice is melting and the butter is not separating, rather melting down into the sludge. 

I have about of month's worth of what I consider medicine in here and I will eat soapy butter chunks if I have to but I'm just wondering if there is some type of secondary wash I can do to get the cannabinoids (or most of them) from the soap/butter/water solution. I was thinking about rubbing alcohol but I'm not sure how that would work or even if it would. 

Any thoughts?


----------



## skillet

Well that sucks, there can't be that much soap in there though can there? I'd probably take a small amount of the butter/water to experiment, try adding lots of warm water to it, stir well or shake it and see if it dilutes the soap enough to help the butter separate. If that works then you can wash it again with more warm, fresh water, and hopefully get most of the soap out.


----------



## A Lucid Pet

> there can't be that much soap in there though can there?


That's what I was thinking! Palmolive concentrated dish soap is pretty good I guess lol. 



> I'd probably take a small amount of the butter/water to experiment...


Thanks! That's a good idea. I'll give it a go.


----------



## skillet

So... what happened?

I'm gonna repeat my earlier question, does anyone have a summary of selectivity for different brain areas of various antipsychotics? Pulling all the info together is going to be a giant pain in the ass, and if someone has already done it...


----------



## Vader

Could GHB form a polymer?


----------



## Iodjini_dk

Yes, but the polymerization works quite poor without a catalyst. I would say under normal conditions it is highly unlikely that GHB will form a polymer.


----------



## Vader

Thanks for the answer. As a follow up, would such a polymer be a substrate for esterases and so be an active prodrug in the same way as GBL is?


----------



## sekio

I think since the polymer unit is small enough it would hydrolize in acid, so I see no reason an enzyme wouldn't speed the process.


----------



## Iodjini_dk

This paper: http://www.sciencedirect.com/science/article/pii/S0142961204009068
Has some info on it. It seems that the polymer hydrolyses into GHB in vivo, but I cant quite figure out if it is fast enough to work as an actual prodrug for GHB. I would imagine the polymer has to hydrolyse fast enough to reach an appreciable plasma concentration of GHB.


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## Vader

How do forensic chemists differentiate heroin from different sources? In particular, how do they differentiate SEA and SA heroin? I understand that the answer to my question might involve synthesis discussion, if so please ignore me.


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## Iodjini_dk

Its close to impossible to remove impurities from the synthesis completely. The character and amount of these impurities depends on many things like reagents, purity of reagents, concentration, temperature, reaction time, method of purification, storage and so forth. You can say that every batch of drugs has its own fingerprint (given that one has the means of analyzing it). This is how forensics can keep track of different batches which can help them trace it back to the source and furthermore ban new precursors.

Its also a great field of interest for pharmaceutical companies as they can investigate the synthesis methods of other companies by analyzing their products. Even pharmaceuticals of very high purity contains trace amounts of synthesis bypr


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## Munroe

from what i've read 5-methyl-mda proved to be inactive.
I've read reports of 2-FA, whats the reason nobody has considered 2-fluro-mda or something similar?
Inactive, instable or too expensive to make?

Or does the same rationale not follow that though fluorination on the 2 position on amphetamine doesn't completely destroy activity wheras it may do on mda?


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## sekio

@Vader: I think it's from alkaloid profiling, different poppy crops have different ratios of alkaloids in them.


I think nobody's made 2-F-MDA because 2-fluorosafrole is hard to come by.


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## Hyperthesis

@Vader: Iodjini_dk and sekio are both right with their answers. To determine the global origin of a heroin sample the following methods are used:

a) Profiling of accompanying alkaloids (as suggested by Sekio), because these very between different strains and not all cultivating countries use the same cultivar. Due to the very long history of traditional poppy-cultivation, the more recent breeding attempts, which aimed at producing poppy variations with preferentially only or few enriched alkaloids, and finally the cultivation of the plant for decorational purposes does the number of poppy-cultivars/-races goes into the hundreds (at least). Obviously, this method is only useful if you know which variation is currently grown in a certain area. This is usually investigated by police raids, taking field samples and checking either the alkaloid spectrum (eg. with GC-MS) or the genotype (more expensive).

b) Profiling of impurities coming from the synthesis (as Iodjini_dk suggested). In the particular case of heroin, this is a bit tricky, because its preparation consists apart from the isolation procedure usually only a single synthesis step. This single step can furthermore be accomplished with a very small range of avaible reagents. I don't think that I spill the beans when naming the most obvious choices: Acetic anhydride and acetyl chloride. For impurity profiling, forensic scientists usually rely on the analysis of residual traces of solvents, auxiliary bases and acids (used for the conversion of the freebase form into salts and vice versa).
In some regions (eg. NZ) certain methods for heroin preparation emerged that facilitate analysis due to their somewhat 'exotic' character. A keyword in this respect is the so-called 'homebake'-method.

c) Profiling of adulterants. The source of a drug is not necessarily limited to its place of cultivation (from the governmental point of view), but also includes trafficking routes. Because adulterants are usually not added at the first level of the production-distribution-chain, adulterant-profiling can help to identify shipping routes or the participation of a certain drug cartel. As a related example, think of the recent rise of levamisole as cutting agent in coke. Adulterant-profiling also helps to distinguish between home-made vs. clandestine-made (ie. large scale) heroin, because for the former readily manufactured preparations are frequently used (pills!). These contain either very specific adulterants (sometimes so specific that one can even name the specific brand, which was employed) or, which is quite suspicious on its own, next to no impurities at all (indicating pharmaceutically pure morphine as source).

Further details are kindly provided by the United Nations: http://www.unodc.org/pdf/publications/report_st-nar-35.pdf


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## Vader

Thanks for the answers guys!


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## television82

What's the chemistry behind benzo withdrawal, and why is their no cross tolerance with the GABAb agonist Phenibut?


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## alkap555

Question A--Chemistry behind benzo withdrawal:

As you prob know, Benzos primarily act as allosteric agonists of the benzodiazepine-GABA(A) receptor complex. Agonizing this receptor effectively increases the net amount of inhibition that occurs upon binding of GABA to it's specific site on the BZD-GABA(A) receptor via increased frequency of chloride ion channel opening. This allows for increased Cl- ion influx into the postsynaptic neuron (mechanism of GABA-inhibition is actually reversed for presynaptic inhibition), which hyperpolarizes the postsynaptic neuron making it more resistant to subsequent depolarizations (makes it more harder to "stimulate" or "fire" which occurs via depolarization. 

Chronic use of benzos lead to downregulation of the BZD-GABA(A) receptor complex via multiple homestatic mechanisms including short- and long-term adaptations likely involving (at first) BZD-GABA(A) receptor internalization (endocytosis). Other long term mechanisms (that I do no know off top of my head) for receptor downregulation are probably involved, but the net effect is the same: reduced BZD-GABA(A) receptor density. Upregulation in opposing neural circuity/neurotransmitters (glutamate etc.) also likely occurs.

When benzos are stopped, the decreased (downregulated) BZD-GABA receptors and GABA neurotransmission in general lead to unopposed excitatory neurotransmission. Subjectively, this is the "benzo withdrawal," and as expected is largely characterized by "opposite effects" of benzos: anxiety, insomnia and many more shitty things.

This withdrawal persists until the homeostatic mechanisms of the CNS re-adjust (upregulate) BZD-GABA(A) receptors and GABA neurotransmission to their original levels. Before this re-equilibration occurs, however, there is a net excess of excitatory neurotransmission which is responsible for the hell of withdrawal. 


Question B--lack of phenibut cross tolerance:

Benzos only bind to a specific subset of GABA receptors known as the GABA(A) receptor (and still only binds a smaller portion of these...the "BZD-GABA(A) receptor complex). Phenibut, is a GABA(B) agonist and has no affinity for the GABA(A) receptors involved in benzo pharmacology. GABA(B) receptors are inherently different, being G-protein coupled receptors rather than Cl- ion channels like GABA(A), and are largely distributed in the peripheral nervous system (more so than GABA(A)) and spinal cord. 

So the two drugs are not cross-tolerant b/c they bind two distinct receptor subtypes... That being said, stimulation of either GABA(A) or (B) has a similar effect of net inhibition and they may be of some use interchangebly in terms of managing withdrawal symptoms. For example, GHB withdrawal (a putative GABA(B) agonist) can be managed with high-dose benzos (GABA(A)), although the gold standard is baclofen (a Rx only GABA(B) agonist)

Sorry if this is not detailed enough or overly detailed....not sure what sort of answer you are looking for. Hope that helps. 
Sources: Graduate degree training in neuropharmacology and neuroscience


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## alkap555

A Lucid Pet:

Sounds like a nasty emulsion you got there. Speaking from experience with liquid-liquid extraction emulsions, they can be a BITCH to break. Sometimes you can dump a bunch of salt in the aqueous phase (salt-out) and that MAY help to break it up, but given that you are working with butter (and soap) instead of clean organic solvents, I'd imagine there isn't much you can do.

Rubbing alcohol will NOT help, as it is both miscible with the water and butter and would worsen the emulsion. If its a small amount of soap I say just eat it anyway, worst it will do is give you diarrhea.

Good luck!


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## Epsilon Alpha

@ a lucid pet:

Dude, this is going to be a bitch seeing as there are a ton of different chemicals in there just to prevent it from forming layers again.
http://www.colgate.com/app/Palmolive/US/EN/Product-Ingredients.cwsp

I'd hazard a guess that maybe adding salt to lower the freezing point of the water MIGHT allow you to have the budder precipitate out if you froze it again which you could then process to see what happens. It would let you remove some of the water if it worked out, but I think you'd still have a soap/cannabinoid/butter sludge left over but more concentrated.


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## ebola?

What was once large and nifty is now Big and Banging

(this thread grew large enough to warrant gestating offspring and heading to the retirement home )

ebola


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