# Stimulants of the Future



## Dope_User

Well, my other thread, "Possible Drugs of the Future" turned into mainly a discussion about opioids, mainly the most potent ones...and I must say, it's extremely informative and interesting.  But unfortunately, all the other classes of drugs seem to have been looked over.

So, what about stimulants of the future?  Are various analogues of amphetamines or other stimulants possible?  Could these are qualities that make them more desirable than say cocaine or methamphetamine?  Even if it's completely theoretical (and unrealistic or would never happen), I'd still like to hear.

Say some type of cocaine analogue (that wouldn't be made due to complexity and it's simpler to just make cocaine from Coca plant) that had even greater euphoria and/or longer duration (say 1-4 hours instead of like 30-45 minutes, depending on person, metabolism, etc.)?

Same goes for methamphetamine.  Any possible amphetamine derived drugs with more euphoria than meth (say an amphetamine or amphetamine like drug with the euphoria of cocaine; I find coke to be more "euphoric" than amphetamines although I know this is subjective)?

And again, same goes for other stimulant-like drugs.  Any way to make some drug similar to Modafinil (sp?) with euphoric properties desirable by stimulant fans?

Lastly, what about a more potent, more euphoric ecstacy (or any MDxx)-like drug?  This one is of particular interest to me.

With any of these, I'd appreciate if you could include "possible drugs" that are more euphoric (may be hard to tell since no one has personal experience), more potent, varying durations of action, or even lower side effect and risks?

Hopefully, you geniuses can go as nuts with this one as you did with the other post and all the great information about opioids?  Thanks in advance for what I know with be some great responses.


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## Hyperion

I can't foresee any cocaine derivatives being introduced because, as you've already mentioned, it's so much cheaper to just grow the stuff than to synthesize it.  Even having a longer duration wouldn't necessarily make it more popular, since generally if people are bothered by cocaine's short duration, they'll switch over to amphetamines.

As for amphetamines, there are hundreds of modifications that can be made to the amphetamine (and related phenethylamine) molecules which are active.  Most of these drugs, however, are psychedelic in nature (ie DOM, DOB, Aleph), and are recounted in PiHKAL.

With opiates, what allows people to create more potent analogues is that minor modifications can allow better absorbtion/solubility and can cross the BBB better without affecting their method of action (ie they're all still mu-agonists).  With amphetamines, the same is true regarding the difference between amphetamine and methamphetamine, but once you get past that minor modification, further changes tend to alter their method of action, increasing serotonergic activity and becoming more psychedelic.  This is a bit of a generalization, since each individual drug is different, but that's the general story.

Now, there are some interesting non-amphetamine substances that have similar effects, like methylphenidate (Rritalin), atomoxetine (Strattera), and Bupropion (Wellbutrin, Zyban).  All three of these substances will increase synaptic dopamine and norepinephrine levels, much as amphetamine will, but are not generally considered to be recreational.  Most of the research into amphetamines tends to be either pharmaceutical companies researching ADHD medications that won't be abused or redirected to the black market, or people like Sasha Shulgin researching the various variations on the phenethylamine/amphetamine structure to produce new and different psychedelic compounds.

As for more potent MDxx drugs, I know Shulgin lists a few in PiHKAL, but as far as I know, none of them were quite the chemical that MDMA was.  The thing with MDMA is that is has some very unique effects, almost a cross between an amphetamine and an SSRI, and part of its popularity is due to the fact that it's not overly powerful (compared to other psychedelic phenethylamines).  Obviously you've probably heard of MDA and MDEA, so there are some possibly alterations that can be done, but neither drug really hits the "sweet spot" that MDMA does in terms of recreational effects.


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## cannabis sativa

> Well, my other thread, "Possible Drugs of the Future" turned into mainly a discussion about opioids, mainly the most potent ones...and I must say, it's extremely informative and interesting. But unfortunately, all the other classes of drugs seem to have been looked over.



you said:



> P.S. If you feel like mentioning other "mind altering" drugs in development, feel free, but please try to keep it to opioids.



you make a thread asking people to please keep the discussion to opioids and then complain that "all the other classes of drugs seem to have been looked over."?  that makes absolutely no sense to me.


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## mitogen

/me visits a philip k. dick -esque amphetamine vending machine. cant remember what short story that was from in particular sorry....


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## mitogen

i think that drugs of the future will actually be cocktails designed to increase specificity to certain pathways. there are SO MANY signalling proteins that are regionally expressed and that alter the activity of GPCR's, g-proteins, adenylyl cyclases etc. etc. 
once we work a few more of them out we'll be able to give really low doses of drug and still acheive the desired effects with few or none of the side effects.


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## BilZ0r

Stimulants I think are one thing that people could hold out some hope for a new, plant derived drug. The monoamine transporters are so promiscuous, it seems all you need is a benzene and a nitrogen somewhere... and your in.


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## Dope_User

cannabis, yeah, I forgot I added that part in other thread...that makes a lot more sense now.  sorry for the confusion.

Hyperion, we both know synthesizing cocaine is basically pointless.  But hypothetical speaking, what could be done to modify cocaine (if someone had a lot of free time on their hands)?


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## Hyperion

I'm not a chemist, so I don't really know what modifications could be made.  I do know that some have been made, which is how we have procaine (novocaine), lidocaine, and benzocaine.   In all three cases, the psychoactive effects of cocaine are completely missing, and these drugs instead act purely as topical anaesthetics.  Someone else will have to explain why this is so.  The thing is, I don't believe that any of these other -caine drugs are as effective as cocaine for topical anaesthesia anyways, given that cocaine is still used as a topical anaesthetic in some surgeries (including, of all things, nasal surgeries).  Unfortunately, I can't seem to find an image of any of these non-psychoactive cocaine derivatives to compare to the cocaine molecule to see where the differences are, otherwise I might have some ideas.  Anyone?


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## Riemann Zeta

Well, cocaine itself is indeed a pointless waste of money.  However, it will always be popular among the wealthy as it is a way of advertising one's vast disposable income.  There are a number of modifications to cocaine that have become popular as radioligands to highlight DAT proteins in PET/SPECT scans.  For example, the WIN 35xxx and RTI series of compounds are tropanes with various non-ester aryl moieties replacing the benzyl ester of cocaine.  RTI-55, for example, is 3-(para-iodophenyl)-tropane-2-carboxymethyl ester and is used with radiolabeled I to trace DA and 5-HT transporters.  It has a duration that is at least 20x that of cocaine.  However, tropanes are a bitch to synthesize, so I don't think that these compounds will ever become popular.  

In terms of reuptake inhibitors, I think that methylphenidate will become even more popular in the future.  However, I doubt that instant-release methylphenidate will still be available or even allowed.  I am sure that all methylphenidate available will be unsnortable, uninjectable, wax-matrix polymer bead based extended release tablets (to prevent "abuse").  In addition, I can see all scheduled medication in the US and UK having RFID police alerting chips in each pill, so authorities can randomly scan peoples' flats, cars, clothing, etc...for stockpiled pills.  Also, as I mentioned in the 'Drugs of the Future' thread, ephedrine will be scheduled soon in the US, leading to the demise of methamphetamine as a street drug and the reintroduction of (dl)-amphetamine sulfate from organized crime syndicates in former Soviet nations.  This, of couse, means the US and UK governments will overreact with a barrage of cruel, vindictive and Orwellian legislation (more-so in the US than in the UK, due to the religiosity of the jesusland freaks).  However, I believe amphetamine proper will never die completely in streets of the US, no matter how many ridiculous laws, obscenely lengthy prison terms and mandatory execution policies are enacted.  

As for future stimulants themselves, I believe that modafinil derivatives are where it's at for the future.  Since modafinil has nill abuse potential and future derivatives of it will have even less, I think that is where pharmaceutical companies are headed.  I think the development of stimulants for ADHD is over, doctors in the EU will not prescribe stimulants right now, period, and doctors in the US have the DEA crawling up their asses, threatening their medical license with every script for Adderall or Dexedrine they give out.  The only new ADHD medications will extremely targeted molecules that work on various cellular protein cascades and carry zero abuse potential and thus do nothing to promote wakefulness or alertness in individuals without ADHD.

In short, all psychopharmaceutical drugs of the future will not be anything that people want to take, only something that people have to take.  They will be neither dysphoric nor euphoric, they will simply be extremely targeted and relatively side-effect free.

Interestingly, this will lead to legitimate (or, more properly, former legitimate scientists) going 'underground' as clandestine chemists and researchers.  Fueled by organized crime money, these will not be Bill-bob and Bubba blowing up the hick-town trailer park while trying to synthesize methamphetamine.  Instead, these will be serious pharmacologists and chemists (likely PhDs and advanced grad students) that are sick of the paucity of funding, squalid lifestyle and restrictive, bureaucratic red-tape that academia brings.


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## defaultused

I'm surprised nobody has mentioned phenmetrazine...


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## Riemann Zeta

Phenmetrazine is too hard to synthesize.  It requires nor-ephedrine, which was banned in 2000.  Same goes for 4-methylaminorex (4-MAX), which is why both are as rare as it gets in the drug world.


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## nenarOPI

Was phenmetrazine part of the phen/fen weight loss combo? If so, i didn't think it had much euphoria?


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## human

Phen-fen was phentermine and fenfluramine, I believe.


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## phase_dancer




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## Riemann Zeta

Fenfluramine is an interesting one...in theory is it an almost purely serotonergic amphetamine.  I would bet that fenfluramine + dextroamphetamine feels a lot like MDMA.


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## Dope_User

http://mdma.net/misc/fenfluramine.html

MDMA vs. Fenfluramine


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## joystick

I have a prescription for phenDImetrazine (phenmetrazine with an extra N-methyl group).  Phendimetrazine is metabolized by the body, according to my Physician's Desk Reference, to phenmetrazine and phenmetrazine N-oxide.  While I enjoy my monthly phendimetrazine fix, it does not compare to methamphetamine.  Neither does Ritalin (methylphenidate) or Adderall (amphetamine).  

I think clear, recrystallized, nearly pure dl-methamphetamine hydrochloride is probably going to remain king of the stimulants for some time.  Its synthesis is easy, it is chemically synthesized from a naturally occurring alkaloid derived from the Chinese ma huang plant, the quality of its high is very good, and the high lasts a long time.  However, I would like to try the heretofore unscheduled 2-benzylpiperidine, a methylphenidate analogue designed to have a much longer half life than methylphenidate, as a possible stimulant.

Cocaine doesn't last long enough for me, is too expensive, and has agonizing come downs.  Plus, the first thing many people do after doing some cocaine is have to take a nasty shit while they are high.  Sure, some cocaine analogues may be very powerful, but they will always be extremely expensive to synthesize as long as they rely on cocaine as their starting material. As for the entactogens, I don't think MDMA / MDA can be beaten either, even though I am on methylone (that is, MDMCAT) right now.  OTOH, I would like to try 3,4-dichloromethamphetamine.

Caffeine and nicotine, two legal stimulants, will probably also continue to be used extensively in the future.  Speaking of nicotinic agonists, I would also like to try ABT-594.

Modafinil and ephedrine are crap drugs in my opinion.


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## Riemann Zeta

Dope_User: The abstract that your link leads to is by Ricaurte, et al.  I don't trust that bloke as far as I could throw him--he was the one using 150mg+ doses of methampetamine instead of MDMA "by mistake" and was forced to recall his paper in Science, right? 

Oh, and phenDImetrazine is quite fun.  I took some (315 mg, sustained-release) a long time ago when visiting a friend in NYC--we went clubbing and were out until 4 or 5 am.  I thought it was a nice feeling, kind of like pure (d)-amphetamine, with no heart palpitations or anything similar.  It did take a long time to kick in, however.  At the time, I assumed it was because the phendimetrazine had to be converted to the first-pass N-desmethyl metabolic product _in vivo_, using the P450 2D6 enzyme.  Reading a review by Rothman, et al (2003), I found out I was right--phendimetrazine is just a prodrug for phenmetrazine.  However, while it was fun for a night, I would never take it chronically for ADD, due to the dangers of primary pulmonary hypertension (a risk with all amphetamines, more pronounced with some of the noradrenergic anorectics).

As for some stimulants/nootropics of the future, here is a little list I have compiled:

Nicotinic Agonists:

ABT-594 (5-(azetidin-2-yloxy)-2-chloropyridine)
Conitine (alpha-keto-oxidized nicotine metabolite)

AMPAKines:

Pramiracetam (out now in the EU, very $$$) & congeners
CX516
CX614 (2H,3H,6aH-pyrrolidino[2",1"-3',2']1,3-oxazino[6',5'-5,4]benzo[e]1,4-dioxan-10-one)
Other Cortex Pharm. Derivatives

Ring-Closed Amphetamines:

2-benzylaziridine
2-benzylazetidine
2-benzylpiperidine
3,4-dichloro-methylphenidate
ethylphenidate
N3-methyl-4-methylaminorex
3-methyl-(1-phenylcyclobutyl)butanamine
N-ethylcathinone

Modafinil Derivatives:

4,4'-dichloromodafinil
pirisudanol (3-hydroxy-2-methyl-5-((4-(2-(methylamino)ethoxy)-4-oxobutanoyloxy)methyl)isonicotinic acid) 

The last one is a particularly odd drug.  It was around in the EU for a while, as a stimulating antidepressant, like bupropion and adrafinil, but I can't find ANY info on it, not even any old journal articles.


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## Dope_User

Riemann Zeta, sorry you didn't find that link to be all that credible.  I simply stubbled across it when searching for anything I could find comparing MDMA to fenfluramine because you have mentioned fenfluramine + dextroamphetamine _may_ feel similar to MDMA.  I must admit, I couldn't tell you the first thing about what scientists/researchers are credible or not...but this new forum is helping.

I would like to hear more about the comparison you made between fen. +d-amp. and MDMA though.  You said fen. is an "almost purely serotonergic amphetamine" and that sparked my curiousity.  Although, I find it somewhat hard to believe that fen. + any amp. could feel similar to MDMA...do you have any info. (other than speculation) about this?  Also, are there any other mainly "serotonegic"amps. (other than those mentioned) that are more potent (in terms of serotonin agonism, release, reuptake inhibition)?  To everyone, what are you opinions on amps. that act strongly on serotonin?  Do these have the potential to be euphoric amps., possibly with some slight hallucinogenic properties (similar to MDMA)?

Riemann Zeta, you also mentioned a couple Modafinil derivatines.  You said prisudandol was prescirbed as a "stimulating antidepressant" and I'm assuming it probably doesn't have much (if any) potential for abuse.  But what about other modafinil derivatives (or derivatives or drugs in the same class)?  Does anyone think such a drug could be synthesized that would be euphoric (such as the first derivative R.Z. mentioned; 4,4;-dichloromodafinil)?

NOTE:  I just did a search for pirisundandol and found info. on "pirisundanol."  I haven't read anything on it yet, but maybe you had a misspelling and that's why you couldn't find any info.


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## Riemann Zeta

You are correct, it was a typo, the name is Pirisudanol.  The compound goes by a number of names, I am not even sure if 'pirisudanol' is the correct one; I have also heard it called pyrisuccideanol.  I remember one of the trade names for it was 'Nadex,' but it hasn't been around for a long time.  

Here is a link for the structure: http://www.psychotropics.dk/usr_vie...Alphabetical+index&historyline=&Catalogtype=A

As for fenfluramine: well, MDMA seems to release NA, DA and 5-HT.  Dextrofenfluramine only releases 5-HT, whereas dextroamphetamine releases NA and DA.  But MDxA (especially MDA) compounds also have affinity for the 5-HT2a receptor, which might contribute to their 'trippiness.'  MDEA ('Eve') is more 5-HT selective than MDMA or MDA, so it might make a better comparison.


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## Dope_User

Riemann, my problem with that comparison was that no one seems to experience any MDxx-like affects from fenfluramine or dextrofenfluramine (at least to my knowledge).  D-amp. releases NA and DA, as do most amps, but it was my understanding this contributes mainly to the stimulant (speed) effects).  Therefore, I'm making an assumption here:  the 5-HT release it likely to be responsible for the 'trippiness' of MDxx compounds.  But if this is the case, then I'd expect dextrofenfluramine and/or fenfluramine to have similar 'trippy' effects, but to my knowledge, they don't.  Maybe they (dextrofen. and fen.) don't have the same affinity for the 5-HT2a receptor, which you say "contribute to their [MDxx compounds] 'trippiness.'"

So, how would combine dextrofenfluramine/fenfluramine (5-HT release) + an amphetamine (like d-amp. with NA and DA release) resemble the effects of MDxx compounds?

Smyth, where can I find the information on the US patent you mentioned?  I link would be greatly appreciated.  Thanks.


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## Riemann Zeta

I wonder if enough people took a large enough dose of (d)-fenfluramine to notice (and report) effects?  The average dose was 10-15 mg when it was still on the market.  Imagine taking 10 mg of MDEA.  Would one feel the effect of that?  Also, I dug up an old (2003) review article by Rothman & Baumann (link below) that had EC50 values of neurotransmitter release (not reuptake, but truly release) for a number of phenethylamines (all in nM):

Phenethylamine:                5-HT; NA; DA

(d)-amphetamine:               1765; 7.07; 24.8

(d)-phenmetrazine:             3246; 37.5; 87.4

(d)-methamphetamine:       736; 12.3; 24.5

(d)-fenfluramine:                 51.7; 302; 10000

(dl)-MDMA:                          56.6; 77.4; 376


So, at least on paper, (d)-fenfluramine and (dl)-MDMA are equipotent 5-HT releasers.  Mix a little (d)-amphetamine into the picture and you've got yourself a party...in vitro, at least.  I wonder what the values for 4-fluoroamphetamine are?

Rothman & Baumann (2003). Eur. J. Pharmacol. 479: 23-40.


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## BilZ0r

But then MDMA seems to release dopamine in some funny way... because its PKC 'dependent' in the striatum, but not in the prefrontal cortex... (1. Damn that paper confuses me. See I'm under the impression that dopamine release in the prefrontal cortex is mediated by 5-HT2A receptor facilitation of impulse dependent release, while in the rest of the brian its because of amphetamine-like action on the dopamine transporter... but that shit doesn't fit very well with that paper, even though its not complete, as they don't use any 5-HT2 receptor antagonists, or any transporter blockers.


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## Riemann Zeta

I always assumed that the propensity of MDMA to release DA was due to its methamphetamine-like character.  Isn't MDMA's affinity for the 5-HT2a receptor rather low, in the micromolar range?  It seems really bizarre that in the striatum, of all places, dopamine release would be dependent on 5-HT2a receptor activation, rather than amphetamine-esque reverse-transport.

One thing I have never seen in press is the affinity of MDMA for the vesicular monoamine uptake transporters (VMAT-1 & -2).   The Ki for (d)-amphetamine is << 100 nM.  I wonder about MDMA?


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## Smyth

Riemann Zeta said:
			
		

> *I always assumed that the propensity of MDMA to release DA was due to its methamphetamine-like character.  Isn't MDMA's affinity for the 5-HT2a receptor rather low, in the micromolar range?  It seems really bizarre that in the striatum, of all places, dopamine release would be dependent on 5-HT2a receptor activation, rather than amphetamine-esque reverse-transport.
> 
> One thing I have never seen in press is the affinity of MDMA for the vesicular monoamine uptake transporters (VMAT-1 & -2).   The Ki for (d)-amphetamine is << 100 nM.  I wonder about MDMA? *



Do you care to elablorate on this please. It looks interesting although I find myself completely unable to comprehend it for the most part.


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## BilZ0r

Yeah, but there is evidence of a distinct paucity of dopamine transporters activity in the (pre)frontal cortex(1), so you can't do an amphetamine like release with no transporter and MDMA-induced dopamine release in the prefrontal cortex tends to be 5-HT2 receptor dependent (to a degree) (2). The source of 5-HT2 stimulation isn't MDMA directly, it's going to be the serotonin (kinda shown by these two papers (3, 4), the effect is weak probably because they are in the striatum, note how in 3, fluoxetines dopamine blocking effects are lost in the slice? Probably because theyre not getting overflow from the cortex).

It's still kinda speculative, but that's how I see it. There's also the possiblity of noradrenergic neurons co-releasing dopamine (5), which complicates things further. Theoretically, you could get a situation where, in the prefrontal cortex, MDMA-is stimulating 5-HT release, which activates 5-HT2(a?) receptors, increasing actionpotential-dependent dopamine release, and MDMA having amphetamine like action on noradrenergic neurons, causing dopmaine/noradrenaline co-release.

(I've never seen a MDMA VMAT affinity either).


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## fastandbulbous

*In vivo!*

So, at least on paper, (d)-fenfluramine and (dl)-MDMA are equipotent 5-HT releasers. Mix a little (d)-amphetamine into the picture and you've got yourself a party...in vitro, at least.  

By taking a drug with a much higher 5HT to DA/NA releasing ratio compared with MDA/MDMA (eg IAP), and adding a bit of amphetamine to the mix (to get a ratio closer to that of the methylenedioxy drugs), you can get afairly good approximation to MDA. I found that a 1:1 ratio of IAP to racaemic (dl) amphetamine got fairly close, but if someone had the materials and inclination to experiment, a variety of subjective effects may be possible; all being an aproximation to a MDxx type experience.


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## xspikehead

*Wrong form of methamphetamine*



> I think clear, recrystallized, nearly pure dl-methamphetamine hydrochloride is probably going to remain king of the stimulants for some time.



Racemic meth is not commonly encountered nowadays. You're referring to the dextrorotary isomer, and trust me, it may be clear and recrystallized, but it certainly is not pure :D


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## nenarOPI

Is there a major difference in effects between racemic methamphetamine and d-meth?


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## Riemann Zeta

L-methylamphetmine has basically no effect other than adrenoreceptor agonism in vivo--it is basically akin to ephedrine in 'psychical intensity,' from what I have read (PNS effects, sweating, rapid HR, BP, etc).  I have never taken any sort of *meth*amphetamine, so I don't really know what either of the feel like, but I'd bet the comparison would be similar to Adderall vs. Dexedrine.


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## nenarOPI

ah okay i thought it was kinda like that, the mixed-salts type thing going on in Adderall. thanks


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## FreyGrimrod

I find it hard to believe that methamphetamine will bow out to amphetamine sulfates easily.... even though I could see the DEA trying to make almonds illegal...


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## xspikehead

> Is there a major difference in effects between racemic methamphetamine and d-meth?



Yes. If you took the same amounts of racemic and stereospecific meth, you would defenitely be able to descern between the two, and you would defenitely notice the high produced from the racemic product is defenitely different. It's still subjective, but pretty much all meth nowadays is _d-_meth.

Tweakers I know were given some racemic meth and initially were disappointed, but later ended up enjoying it just as much and in half the cases even more. This is attributed to their reports of a weaker but more euphoric high and a less exhaustive and shorter lasting comedown. All tweakers pretty much reported that tolerance levels remain identical between the two types.

Since everyone's had _d-_meth and only very few have had racemic meth, technical information probably won't do you any good. And unless you used meth in the '70s and up to the late '80s, you likely have never had racemic meth and likely never will. It truly is the superb product in my opinion in every aspect, and most tweakers given the product ended up in agreement with that statement.


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## fastandbulbous

*Possible new directions*

As the legal side catches up with the experimental chemist, it means you have to cast your net further afield in order to "catch" more useful (but as yet uncontrolled) stimulants. I reckon some of the field with really rich pickings are derivatives of phenmetrazine, fencamfamine and pipradrol.

Starting with phenmetrazine






Now phenmetrazine, is quite well known as a drug of abuse, but when people think of phendimetrazine, they tend to think of 2-phenyl-3,4-dimethylmorpholine (one of the methyl groups being attached to the nitrogen atom); this isn't too hot as a stimulant. If the second methyl group is moved to the 6 position (cmpnd 2) though, you end up with a compound that has the same potency as phenmetrazine, but isn't yet controlled. Or alternatively, you can replace the oxygen with a methylene group, to give 2-methyl-3-phenylpiperidine (cmpnd 3). This doesn't release dopamine as phenmetrazine does, but is actually a reuptake inhibitor (similar mechanism to methylphenidate). One other alternative is 2-methyl-3-phenylquinuclidine, which is also a reuptake inhibitor (no dosage info for last two, only that they are active; cmpnd 2 is same dose as phenmetrazine, namely 25mg)

Fencamfamine also lends itself to a lot of fiddling and tweaking of the basic skeleton






Both 2-phenylcyclohexylamine and 2-phenylcyclopentylamine are active CNS stimulants at 20mg, although this is a two fold drop in potency when compared with fencamfamine (10mg), although N-methylation of the amine function might give some increase in activity; cmpnd 4 is active, but alas, no dosage data for that one either. All four compounds are unusual in being both dopamine releasers and inhibitors of its reuptake (and fencamfamine is probably the smoothest stimulant I have ever tried - absolutely no peripheral activity such as increase in heart rate)

Pipradrol derivatives are the one where most hope lies.






Shulgin wrote about 2-(diphenylmethyl)piperidine as being a possible future drug of abuse, as it is estimated to have the same CNS stimulant properties as methamphetamine, but to be active at 2.5mg as opposed to 5mg for methamphetamine, and also to have less peripheral activity as well. It's a bit more complicated to synthesise than meth from pseudoephedrine, but once governments have finished trying to stop bathtub meth manufacture, it may become a possibility for some chemists. Pipradrol os active at 2mg, but is not a strong stimulant (prob because of the tertiary alcohol group - remove it to get 2-(diphenylmethyl)piperidine). The pyrrolidine analogue of pipradrol is also a CNS stimulant, similar to pipradrol and active at 5mg (it was offered by one of the research firms that were closed by Web Tryp), and as with pipradrol, almost all of the activity was present in one optical isomer only. Finally to the great hope that is 3-(diphenylmethyl)morpholine. In a paper where a whole series of diphenylmethyl derivatives of heterocyclic rings werte produced , it was the most active of all the compounds teste; should have an active dose in man of around 1mg, and similar in effect to the compound Shulgin favoured: And the best bit, it can be synthed from the synthetic amino acid diphenylalanine (which is fairly available) by reduction to diphenylalaninol, reaction with 2-iodoethanol, then ring closure to the morpholine by removal of a molecule of water by conc sulphuric acid (same way phenmetrazine is synthesised). It would definitly be worth considering for a chemist with a desire to create (and it's not controlled... yet).


One last bit for the cocaine lovers among you. 







The 3-alpha-phenyltropane with an acetylated 2-hydroxy group in the axial position has been assessed as being 60x the potency of cocaine, with a fairly similar pharmacological profile (ie abusable, unlike the Win series compounds with an axial 2-methylcarboxyl group). I remember reading that the unesterified compound is less active, but still moreso than cocaine. The OH goup must be axial to the ring though, or its potency becomes a fraction of that of cocaine's. 

The last two are very simple compounds that are esters of pseudotropine. The benzoate ester is also known as tropacocaine and has a potency of about 0.1x that of cocaine. replacing benzoic acid with 4-fluorobenzoic acid gives a compound of aprox 0.4x the potency of cocaine; considering how easy it is to synth (and not from monitored reagents - you can actually start from atropine and get to 3-pseudotropyl 4-fluorobenzoate in a few easy steps), I'm really surprised that it hasn't shown up in street cocaine. Maybe the market is so saturated that no one thinks it's economically viable


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## Riemann Zeta

Since I didn't think one could attach files, I didn't include structures of my stims of the future before, but here they are now:


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## Riemann Zeta

The synth of _N_-benzhydrylpropan-1-amine is even easier than that: diphenyl ketone & n-propylamine under reductive conditions (NaBH3CN or another weak reducing agent should do).


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## fastandbulbous

Riemann Zeta:

Are the benzhydrylamine derivative reutake inhibitiors, as I've never come across them as CNS stimulants (except in a long and winding way, via 1-benzylpiperidine - if you see what I mean). Do you have refs?

Can't say I would hold too much store by 2-benzylaziridine, and poss 2-benzylazetidine, as the ring stain of three and four membered rings makes them too dodgy as DNA (or whatevers around!) alkylators. 1,2-dimethyl-3-phenylaziridine is a by product of meth synthesis via RP/I synthesis route, and it's very toxic (will truely fuck your kidneys). I know of one person at least who's come a cropper from it.

Of the others, ethylphenidate is only about 20% as effective as methylphenidate as a stimulant (there is a paper somewhere about higher homologue esters derived from methylphenidate stating that, but I can't for the life of me remember the ref. Might be worth searching). Ethcathinone is fairly effective, between tyhe potency of methcathinone and diethylpropion (got to try it many, many years ago), but the one I really hope is effective is 2-benzylpiperidine; if it is effective, then 3-benzylmorpholine should be as well, and it can be synthed by reducing phenylalanine, then using 2-iodoethanol in ring closure, by the same method as phenmetrazine. By starting with D or L phenylalanine, you can even make specific optical isomers (ho ho!).

The others look interesting, but I can't say that I know that much about them. If you're after reuptake inhibitors though, apparently 4-benzhydrylpyridine derivs are quite effective, but all the refs are on the unmentionable site.

Purchase of 2-carboxymethyl pyrrole [proline] followed by the addition of two equivalents of phenylmagnesium bromide would be an easy ticket for the unambitous hobbyist. 

Smyth:

If you're really lazy (hell I am, given the chance!), you don't even need to synth the pyrrolidine analogue of pipradrol. You can buy it ready synthed (as separate optical isomers), if you know where to look, as it's used for resolving optically active alcohols. It's actually not bad as a stimulant; doesn;t destroy your appetite, and very little jaw tension; just it lasts a fuckin' long time, which you don't always want (as part of my lazy side, I do like my sleep).

PS proline is pyrrolidine-2-carboxylate, not pyrrole, bur I know what you mean.


----------



## Riemann Zeta

You might be right about the small heterocyclic ring-closed amphetamines, I just threw them out there because they are similar to the MAO-A inhibitor called tranylcypromine, which is a non-heterocyclic cyclopropyl amphetamine derivative (b-ethyl and a-methyl carbons are linked)--I've always wondered if tranylcypromine has any alkylating activity.

As for ethylated stimulants, the one article that I read on ethylphenidate (a long time ago) mentioned that it was about equal in potency to methylphenidate and longer lasting (a plus).  I'll try to dig up a ref.

Ethylcathinone is the active metabolite of diethylpropion.  Much like phendimetrazine, diethylpropion is inactive by itself, but is converted to ethylcathinone by first-pass metabolism.  So I would imagine that ethylcathinone would be like super-fast acting diethylpropion.  I have never taken any diethylpropion myself, what is it like?     

The 3-benzylmorpholine compound you mention is indeed fun looking.  However, I don't see how you get it with phenylalanine and 2-iodoethanol (without, maybe a super strong acid).  Perhaps reduced phenylalanine (yuck, LAH!) and 1,2-dichloroethane?


----------



## Smyth

You dont like LiAlH4? It is used pretty frequently in organic chemistry you know. The problem is that it doesnt last very long maybe 1 year tops.


----------



## Riemann Zeta

I know LiAlH4 is used frequently and I have used it on a number of occasions.  It is, however, a fairly dangerous reagent in terms of its toxicity, reactivity, explosiveness, etc.  Due to the *tremendous* amount of caution that must be exercised to use it safely (N2 atmosphere, dry THF solvent, blast shield), I would rather avoid all the hassle and use something more mild like NaBH3CN.  Besides, milder reagents are more friendly to sensitive molecules and give fewer side products.


----------



## fastandbulbous

Subjectively, diethylpropion seems to supress appetite by producing butterflies in the stomach (it's not subtle, by any means). Ethcathinone was smoother (didn't seem to come on any quicker), but still a bit rough around the edges; think it's because one of the metabolic routes reduces the keto group to an alcohol and voila, you've got an ephedrine derivative (barely supresses wretch at thought of ephedrine!)

Tranylcypromine isn't an alkylator as the three carbon atoms don't have much in the way of charge separation going on, hence fairly stable (well stable compared with most three membered ring structures). Replace one of the carbons with a heteroatom like nitrogen or oxygen, and you've got a fairly pronounced case of charge separation, making the ring a lot more susceptable to ring opening via addition reaction (a bit like addition reactions to alkenes, but a lot more pronounced)

The 3-benzylmorpholine sequence:

phenylalaninol + 2-iodoethanol = 3-phenyl-2-(2-hydroxyethylamino)propanol

then ring closure via dehydration using conc sulphuric acid (or similar strong dehydrating agent). Removes water from two hydroxyl groups to form an ether; in this case, morpholine being a sort of cyclic ether. Instead of using 2-iodoethanol, you can use ethylene oxide, but it's a bit more difficult to work with.

You could start from phenylalaninol, but it rather defeats the simplicity of starting from an amino acid. I do share your feelings about lithium aluminium hydride though (and sodium hydride, sodamide etc...). Nasty little buggers.

One last thing; nobody's mentioned alpha,beta-dimethylphenethylamine (3-phenyl-2-butylamine) and it's N-methyl deriv. They're fairly effective, uncontrolled (at least in UK) and for anybody going to the bother of synthesising benzyl methyl ketone (BMK, phenylacetone) for amphetamine synthesis, it's exactly the same route, but instead of starting with phenylacetic acid (which is watched), you start with 2-phenylpropionic acid (which isn't). You could even get away with starting from 2-phenylpropionitrile (1-phenethyl methyl ketone might be seen as taking the piss, as anything even slightly like benzyl methyl ketone had chance to be kept note of, if not activly watched)


----------



## Smyth

Well LiAlH4 does not have to be used under a nitrogen atmosphere in the same way that BuLi must be used under Schlenk line. I am not saying that I like using it because it does have associated risks. However from a synthetic standpoint they are literal god-sends. How do you reduce an ester without LiAlH4? 

Back to the job at hand. Yes, why reduce it yourself when you can actually buy phenylalaninol. Uh ive been looking at Sigma & its not cheap! Cost does have the propensity to affect things, undoubtedly. Plus the morpholone ring forming reaction looks difficult, I bet that cant be high yielding. Also these products are all phenethylamines. Technically atleast they are all illegal.


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## fastandbulbous

Plus the morpholone ring forming reaction looks difficult, I bet that cant be high yielding. Also these products are all phenethylamines. Technically atleast they are all illegal. 

The ring closure using conc sulphuric acid is both easy and high yielding (hunt down phenmetrazine synth and you'll see). Basically it involves a two hour reflux and voila, ring closeure to a morpholine

Also, how do you think that they are illegal? Unlike the US, with it's controlled substance analogue act, here in the UK for a chemical to be controlled, it either has to be specifically named, or covered by one of the coverall paragraphs for Class A drugs. Psychedelic phenethylamines have a coverall paragraph, but even in that case, the had to add some named compounds from PIHKAL, because of how specific that part of the act is; as far as phenethylamine derived stimulants go, there is no coverall paragraph, so if it's not specifically named, it's not controlled. The only controlled stimulants named that contain a morpholine ring are phenmetrazine and phendimetrazine


----------



## fastandbulbous

^^ nope, just the ones that fall under the tryptamine and phenethylamine derivatives paragraphs (I'll stop using coverall, as they obviously don't), and they're just for psychedelics. The scope for straight stimulant compounds is wide open (until they decide to concentrate on them!)


As far as the synthetic chemistry goes, I hung up my leibig a long time ago, due to LE visits, galloping paranoia and most importantly, I promised my other half I would before we got hitched. Getting a promise out of me is like pulling teeth, mostly because if I do give my word, it's because it's an absolute on my behalf.

Doesn't stop me passing on what knowledge I gained beforehand though (plant extractions not coming under synthesis either!)

BTW Racemic-SYN-4-(3,4-dichlorophenyl)-3-carboxymethyl-methylpiperidine SUX!  

Actually, it sounds like it would have potential as an antidepressant _a la_ amineptine, which, from what I've read, is rather pleasant


----------



## Smyth

I have a recent article on ritalin SAR's (2001). In this particular article the focus was on exploring heterocyclic rings other than piperidine. Neither morpholine nor any of the other ring sizes threw-up any suprises. But, I understand (from what I have read on BL) that for ritalin the benzylic -CO2Me is easily metabolized off. In fact I thought it was due to this reason that it is short-acting.

I have got a backup file for the document that was in the 'Novel Discourse' section of the hive from a few months ago. From the discussion there I gathered that the morpholine ring is the most potent in its class, more so even than the corresponding piperidine compound.

Looking back at this, it was the *di*phenylalaninol that this was based on, phenylalanine derived molecule was merely hypothetical. It is no suprise for me that swapping the CO2Me in ritalin for a benzene would give a fully active compound with a lowered 'buzz' potential that is long lasting. 

But this business of the morpholine ring being more active than the piperidine ring is confusing to say the least. Please explain..


----------



## fastandbulbous

*It's me again!*

The bit you took from the Novel Discourse was actually the bits that I posted; they were a sort of condensed down verson of some of the research I did while doing my M.Sc. (SAR of anorectic agents). As for why the morpholine ring is more potent than the piperidine ring, I haven't a clue; as they are not anorectic agents, so my delving into their action came to a halt at that point.

PS hydrolysis of the methyl ester group is the main metabolic route for deactivation in man. Replacing the carboxymethyl group with a straight acetyl group (to give a ketone) might work to extend activity - it works for opiates (hydroxypethedine vs ketobemidone)


Oh one other thing that I found after grubbing through my old stuff:

O-acetylephedrine is quite a potent stimulant (and appetite supressant) that is free of all the nasty, shitty peripheral effects of ephedrine. The only drawback is that it's unstable, and if it encounters an alkaline enviroment, the acetyl group transfers from the oxygen atom to the nitrogen atom.

It's potency though, is due to masking the polar OH group by esterification with acetic acid. Just a thought, but O-methylephedrine might well be a potent stimulant for the same reason (and easy to produce, and stable: treat ephedrine with a strong base like sodium hydride or sodamide, then add a molar equivalent of methyl iodide and _voila_)

Anybody ever seen anything about O-methyl ephedrine or phenylpropanolamine?


----------



## fastandbulbous

Riemann, my problem with that comparison was that no one seems to experience any MDxx-like affects from fenfluramine or dextrofenfluramine (at least to my knowledge). D-amp. releases NA and DA, as do most amps, but it was my understanding this contributes mainly to the stimulant (speed) effects). Therefore, I'm making an assumption here: the 5-HT release it likely to be responsible for the 'trippiness' of MDxx compounds. But if this is the case, then I'd expect dextrofenfluramine and/or fenfluramine to have similar 'trippy' effects, but to my knowledge, they don't. Maybe they (dextrofen. and fen.) don't have the same affinity for the 5-HT2a receptor, which you say "contribute to their [MDxx compounds] 'trippiness.'" 

MDxx compounds don't have much of an affinity for the 5HT2A receptor (compounds that do produce the classic psychedelic experience, as opposed to the entactogen effects (empathy, abolition of anxiety etc) that MDxx compounds produce). They do cause a huge efflux of serotonin from pre-synaptic storage vesicles, which will interact with all of the 5HT receptors to some degree.

The difference between MDxx compounds and dexfenfluramine is that MDxx compounds also have quite a large effect on dopaminergic neurones as well as serotonogic ones, whereas dexfenfluramine acts almost exclusivly through serotonogic mechanisms. To that extent, it is most probably quite like comounds like 3-methoxy-4-methylamphetamine and 5,6-methylenedioxy-2-aminoindan. IAP has more dopaminergic activity than those two, but it's still a long way from MDA like activity. IAP and amphetamine together do produce quite a pronounced MDA like activity, but I wouldn't even consider mixing dexfenfluramine with amphetamine due to reported cases of pulmonary hypertension.


----------



## Riemann Zeta

Granted, combination of (d)-fenfluramine and (d)-amphetamine would not be very wise due to pulmonary hypertension and/or arrhythmias / torrsades de pointes (sp?) danger.  From a purely theoretical standpoint, however, I think we are making the same point--the effect of MDxA compounds is mainly due to massive 5-HT and DA (and NA, the poor neglected bastard stepbrother of DA ) release.  Since (d)-fenfluramine releases _only_ 5-HT and (d)-amphetamine releases NA and DA, I bet they would feel similar.  However, that is kind of tangential to the 'Stimulants of the Future' title, so sorry for drudging it back up.


----------



## fastandbulbous

*Another tangent to off-topic subjects*

I just had a thought about modification of stimulant skeletons that might open up an interesting side topic. The entactogen drugs originally came from modification of a stimulant drug (amphetamine) by sticking a methylenedioxy group onto the phenyl ring, but there are another group of modifications that produce drugs with entactogen activity, but have never found wisespread use due to their neurotoxicity; namely the 4-haloamphetamines and N-methyl derivatives.

I've read mixed things about 4-fluoroamphetamine, but in things like the 4-halo 2C-X compounds, the fluorine derivative isn't really representitive of the other halogens (2C-C, 2C-B & 2C-I). Equally, 4-bromoamphetamine, 4-iodoamphetamine and the N-methyl derivatives seem to have profiles a lot more like that of MDA/MDMA than 4-fluoroamphetamine, but are quite neurotoxic in all studies.

Developing an idea I had regarding the 2-fluoroethyl group as a replacement for bromine in 2C-B to give 2C-EF as a possible, non-scheduled (in the US, at least, if not the UK) equivalent to 2C-B, I wonder what sort of properties 4-(2-fluoroethyl)amphetamine and 4-(2-fluoroethyl)methamphetamine would have. The 2-fluoroethyl group is a pseudohalogen, in that it has the same effect on the electronic configuration of the aromatic ring, as say a bromo or iodo group. So by extension, I would guess that 4-(2-fluoroethyl)amphetamine and 4-(2-fluoroethyl)methamphetamine would have a similar pharmacology w.r.t. 5HT and dopamine as 4-bromoamphetamine/4-bromomethamphetamine, but becase of differences in the size of the group etc., could possibly not be neurotoxic. This would lead to a couple of new serotonogic, entactogen drugs without the methylenedioxy ring (which would be a gift to clandestine synthetic chemists - no reliance on safrole). From what I remember from studies in rats, the 4-bromo derivatives are 3x the potency of MDMA in their effects on 5HT and dopamine.

Mind you, it's also possible that 4-fluoroethylamphetamine might turn out to be as neurotoxic in humans as well, or as equally dangerous as 4-methylthioamphetamine (MTA) because of MAOI activity; so any refs or info regarding 4-chloro/bromo/iodo amphetamine/methamphetamine pharmacology would be appreciated (I very much doubt if there is anything out there about 4-(2-fluoroethyl)amphetamine, other than a possible synthesis).

I know it's a bit of a long shot, but unlike the psychedelics and stimulants, there aren't many drugs out there that are primarily entactogens. We definitly need more of them to choose from/work with


----------



## Riemann Zeta

Beyond the 4-fluoro analogue, _para_-halo substituted amphetamines seem to have a high selectivity for 5-HT release and also seem to cause 5-HT neurotoxicity.  This seems to be the case for any electron-withdrawing moiety in the 4- position, such as -OMe (PMA), -SMe (4-MTA), etc...  For example, _para_-chloroamphetamine (PCA) is used to ablate 5-HT neurons in experimental animals.  I assume that 4-bromoamphetamine and 4-iodoamphetamine are similar to PCA--neurotoxic 5-HT releasers.  

N-alkylation adds a new dimension to the picture, however.  Phenomenological reports (one on this sight in Trip Reports, I believe) have shown that 4-methoxy-N-ethyl-amphetamine (PMEA) has an empathogenic-like effect.  Studies have also shown that N-alkylation reduces the toxicity of 4-methoxy substituted amphetamines, rendering PMMA less toxic than PMA and PMEA less toxic than PMMA.  Based upon this, 4-bromo-N-ethyl-amphetamine (PBEA) might be a really interesting compound.  In fact, an old (and I mean old), study demonstrated a cross-tolerance between 4-bromo-N-methyl-amphetamine (PBMA) and LSD:

Knoll J, Vizi ES (1970). Cross-tolerance between para-bromo-methamphetamine (V-111) and LSD-25. _Pharmacology_. *4*: 278-86.

I wonder if this cross-tolerance would extend to MDMA?  Also, your point about MDMA having both stimulant and empathogenic effects is an interesting one.  Can the two psychical effects be teased apart?  A number of people assume that MDEA (Eve) is more of a pure empathogen and less of a stimulant than MDMA or MDA.  I wonder if this is true?  MDEA is more selective for 5-HT release than MDMA, if I recall correctly.  

In addition, if one wanted a true empathogen, modification of the vesopressin/oxytocin peptidergic system would add to the effect of a serotonergic amphetamine.


----------



## fastandbulbous

Beyond the 4-fluoro analogue, para-halo substituted amphetamines seem to have a high selectivity for 5-HT release and also seem to cause 5-HT neurotoxicity. This seems to be the case for any electron-withdrawing moiety in the 4- position, such as -OMe (PMA), -SMe (4-MTA), etc...  .

I wasn't aware that any studies have documented neurotoxicity of PMA and MTA. I know PMA is cardiotoxic, but that's got more to do with adrenergic stimulation; MTA was originally claimed to be a non-neurotoxic MDMA like agent, it's just that _in vivo_, MTA is an MAOI, and the overall toxicity is linked to serotonin syndrome produced because of the MAOI activity.

That's why I thought 4-(2-fluoroethyl)amphetamine might turn out to be a useful entactogen (barring it having MAOI activity - the cardiotoxic effects of PMA seem to be directly linked to the 4-methoxy group, and the fact that an oxygen atom on the 4 position confers all sorts of adrenergic activity)


----------



## Smyth

I finally tossed my copy of PIHKAL a coupke of months back. I think I recall seeing something similar to this there (DOEF or some such compound). Slight road-block may lie in the availabilty/cost of starting materials. But I agree sort of that it might be an idea.


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## hydrobromide

BREAKING SYNTH RULES


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## Dope_User

I don't know if this is in any way related to bydrobromide's question, but are there any modifications that could be made that would have any of the following effects: increased potency, different duration of action/half life (both longer and shorter), increased euphoria (not sure you can answer this without any type of experiment/actual usage...but if it is possible to determine, I'm sure some of the bright minds on here could do it).

I just wanted to point out that the title, "Stimulants of the Future" may not be the best title for this thread...as I'm really not concerned about what are the most probable stimulants that we will see in the future.  Rather, I'm looking for any possible stimulants, regardless of difficulty of synthesis or even ones that would NEVER be made (due to whatever circumstances would prevent them from being made).  Ideally, I'd like to know the "most euphoric" possible stimulants, regardless of anything that would prohibit them from being made (i.e. difficulty of synthesis, difficulty obtaining precursors, illegality, etc.).  Just wanted to make that clarification.


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## Riemann Zeta

That really depends on your definition of 'psychostimulant.'  If you mean "a compound that keeps one awake," then the di-chloromodafinil compound that I suggested might have the greatest potential.  If you mean "a compound that causes a 'euphoric' rush" then I don't know if anything more 'euphoric' than (_d_)-methylamphetamine can be made.  However, what do you mean by 'euphoria,' as that term has different meanings to different people.  Some people think that (_d_)-amphetamines are the most euphoric compounds out there, due to the mental clarity and 'rush' engendered by them.  Others prefer a more serotonergic amphetamine, such as MDMA, with its empathogenic feelings of 'romantic or spiritual love.'  Others seem to prefer the quick up/down effects of cocaine and methylphenidate, in which case, dichloromethylphenidate has the greatest potential.   

With respect to the 4-hydroxyl derivatives of methamphetamine and methylcathinone, I don't think that a 4-hydroxyl derivative would be lipophilic enough to cross the BBB.  Perhaps a 4-halo derivative of methylcathinone would be interesting.


----------



## hydrobromide

Riemann Zeta said:
			
		

> *With respect to the 4-hydroxyl derivatives of methamphetamine and methylcathinone, I don't think that a 4-hydroxyl derivative would be lipophilic enough to cross the BBB.  Perhaps a 4-halo derivative of methylcathinone would be interesting. *



The reason I asked was I found some information on 4-hydroxy-methamphetamine, specifically saying that it was an active metabolite of methamphetamine. How active, and whether or not it would even be worth it to experiement with is beyond me...


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## fastandbulbous

If the hydroxy group is added after crossing the NNN, then it will have some central effects; if it's metabolized outside the BBB, then the effects it will have will be the same as stimulation of the sympathetic NS (increased heartbeat, dry mouth etc)


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## Riemann Zeta

NNN?


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## Smyth

Presumably he hit the wrong key by accident. 

Wrt to dichlororitalin, I have a patent where the nitrogen atom becomes an oxygen atom. The starting material used is thus tetrahydrofuran. I'll post details in a little while.


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## kaoskid

i would like to see an mdma 4-methylaminorex hybrid (you could call it MDAX) also, if you can find a mirror of the old rhodium site there was a great pdf dealing with cocaine analogs.


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## Smyth

If anybody does want to know more asbout this then read the attached link: http://patft.uspto.gov/netacgi/nph-...&s1=Indatraline&OS=Indatraline&RS=Indatraline

Happy reading


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## C6H6

There are many very potent dopamine/monoamine reuptake inhibitors which have no recreational value whatsoever. Mazindole and bupropion are good examples. And just because a compound has a stimulant effect in mice or rats doesn't mean it has recreational value. I've made quite a few compounds which are stimulants for rodents but are useless for humans. Finding good new stimulants isn't as simple as it might seem.


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## C6H6

I'm surprised nobody mentioned amfonelic acid yet. It's a well documented, potent stimulant. One publication even concludes that it's more addictive than morphine.


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## Smyth

*Finding good new stimulants isn't as simple as it might seem.*

I totally agree. Deutsch predicts on the basis of discrimination ratios (binding affinity / uptake inhibition) that dichlororitalin is the most addictive of all ritalin analogs. However it could easily turn-out that dichlororitalin is a piece of shit, we just dont know that in advance on the basis of tests conducted on rats & theoretical models alone.


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## BilZ0r

> There are many very potent dopamine/monoamine reuptake inhibitors which have no recreational value whatsoever. Mazindole and bupropion are good examples. And just because a compound has a stimulant effect in mice or rats doesn't mean it has recreational value. I've made quite a few compounds which are stimulants for rodents but are useless for humans. Finding good new stimulants isn't as simple as it might seem.



Well I'd geuss bup is no fun because it has slow distribution kinetics, and it is too DAT selective (and possible has too low SERT affinity)... While Madizanol, I'm not sure why it's not fun... maybe its TOO NET selective...

It would seem to me, that for a reuptake inhibitor to be fun, it needs to be quite equal SERT/NET/DAT...

While amphetamines need to be leaning towards NET/SERT.


----------



## C6H6

I don't think it's a matter of selectivity. The best explanation I've found so far is this:

Mol Pharmacol. 1994 Feb;45(2):312-6. 

Release of dopamine via the human transporter.

Eshleman AJ, Henningsen RA, Neve KA, Janowsky A.

Research Service, Veterans Affairs Medical Center, Portland, Oregon.

A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage and release mechanisms. Cells expressing the dopamine transporter acquired the capacity to take up and release dopamine via the transporter. Ionic conditions that stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low concentrations of extracellular Na+, were found to stimulate Ca(2+)-independent release of [3H]dopamine from transfected COS-7 cells. Dopamine uptake inhibitors had one of three effects on transporter-mediated efflux. Some drugs, in addition to inhibiting uptake, inhibited spontaneous release of dopamine. Drugs in this class included mazindol, GBR-12935, bupropion, nomifensine, and benztropine. All of the drugs with the potential for abuse by humans either enhanced release (methamphetamine, amphetamine, and ethanol) or had no effect on release (phencyclidine, cocaine, and WIN 35,428). The ability to define classes of uptake blockers based on their effects on human transporter-mediated dopamine efflux may lead to the identification of structural features of the transporter that differentiate abused from nonabused drugs.

PMID: 7906856


----------



## Dope_User

> It would seem to me, that for a reuptake inhibitor to be fun, it needs to be quite equal SERT/NET/DAT...
> 
> While amphetamines need to be leaning towards NET/SERT.



BilZ0r, I was under the impression that the affects on dopamine are the primary reason why amphetamines are "fun."  Could you explain why you say that it "need to be leaning towards NET/SERT?"


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## BilZ0r

Because it seems that there is either low DAT expression and/or function in the prefrontal cortex. 

Also, if you just block a single transporter, it seems that the monoamine is taken up by the others, you still get an increase, but not anywhere near as big.

Check out this little review on the subject.


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## yaesutom

bump

i heardd the wordd from da lord, and da lord said, fellow lord that mdpv stuff might return but there's probably a hundred DA uptake inhibitors possible that are selective and similar, but more euphoric and less higher dose side effects, and maybe easier and cheaper to make too.  I'd eat some.  Yum.


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## cynosure

Riemann Zeta said:
			
		

> Phenmetrazine is too hard to synthesize.  It requires nor-ephedrine, which was banned in 2000.  Same goes for 4-methylaminorex (4-MAX), which is why both are as rare as it gets in the drug world.


Real pitty. I remember the day I went to he druyg store and the cold meds section was "missing". The day they pulled phenylpropanolamine off the shelves. I don't know why there wasn't more 4-methylaminorex on the market when PPA was so readily available. I guess there wasn't an easy synthesis known at the time. I've read that going by the same route, but using psuedo(ephedrine) produces an aminorex derivative that has some negative effects on humans. Does anybody know more about this? Because 4-methylaminorex is one of the easiest synths out there, if you have access to PPA/nor-ephedrine. And ephedrine is still readily available, it would be great if one could cyclize your ephdrine and make something effective and non toxic. I'm pretty sure that the synthesis wouldn't need any major tweaking to produce the (un)desired aminorex. I'm sure there are other people that have thought about many other aminorex analogues, probably largely academics. Personally, I would love something that lasted about 3 times less long than 4-mar. I remember one of the first times I took 4-mar (I don't know which isomer) but I was up for 3 days. One dose, no binging. There wasn't ever a second in those three days that I wanted to do more. There were times where I wished I had done less. but wow. Long lasting. 
i think something that I'd like in a stimulant is the property like this: After your dosed, you can sleep after 3-4 hours. Cathinone is a winner for that one. Too bad you have to take so much of it.


----------



## yaesutom

Anyone have any info about the different isomers of 4-MAR and comparisons to their subjective effects?  I tried the cis isomer a while back, thats one wierd stimulant... and yep lasts a looong time.


----------



## cynosure

yaesutom said:
			
		

> Anyone have any info about the different isomers of 4-MAR and comparisons to their subjective effects?  I tried the cis isomer a while back, thats one wierd stimulant... and yep lasts a looong time.



Yeah, I've got a link to some discussion about the different effects of the differing isomers. But the bookmarks aren't on the computer I'm on now. I'll send them when I have a chance. in this discussion they also discuss the ephedrine analogue of 4-mar. I know that's not very clear. basically they discuss what you would get if you substituted ephedrine for phenylpropanolamine. I'll look it up.


----------



## fastandbulbous

> Phenmetrazine is too hard to synthesize.



Actually it's quite easdy, it's just getting the norephedrine/phenylpropanolamine that's the difficult bit. If you do have the norrph., then it's less complicated than making meth from ephedrine


----------



## watch

So I read through, and I really enjoyed this thread and the wonderful collection of knowledgeable folks here on bluelight... but, still, one nagging question remains...

h0w culd i make meth? & lsd???


----------



## Black

watch said:
			
		

> So I read through, and I really enjoyed this thread and the wonderful collection of knowledgeable folks here on bluelight... but, still, one nagging question remains...
> 
> h0w culd i make meth? & lsd???



lol. you could not if you have to ask how.
i wonder how long you're going to stay here on bluelight 8)


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## watch

It's a joke, my friend. I felt the thread was lacking without the "teach me how 2 make drugs" post.

It's a beautiful contrast, don't you think?


----------



## robatussin

i think....no


----------



## kakti

My dog mentioned to me that the vet prescribed her PPA pills for her uncontrollable bladder


----------



## watch

Lighten up fella


----------



## hugo24

Does anybody know N-Ethylamphetamin?Information appears extreme sparse on this one.


----------



## EN21

*fascinating MAR*

Sorry, I never heard about it, but I have an other question:
The closer I look at the MAR, the more surprising things catch my eyes:
Do I look right, if aminorex can be seen as a rigidisized PEA molecule and 4-MAR as the amphetamine (or even methamphetamine) counterpart. What nitrogen will be more basic and will interact with the receptor? (mind the possible tautomerisation) No idea, but to me it sounds reasonable. In that case it really would make sense to try further substituents at the aromatic moiety. (e.g.: methylendioxy- or 2,5-dimethoxy 4-any other thing, or even an indole). It could also be seen as an hydrolytic stable O-acetyl-norephedrine.
Just an other comment to the fluoroethyl substituents. Care should be taken, since most of fluoroethyl-containing compounds probably form fluoroacetic acid as a metabolite. It is highly toxic. For references see: http://www.fluoridealert.org/pesticides/fluoroacetic.acid.toxnet.htm 
If the active dose of the drug is considerable low, this should not matter.


----------



## Smyth

Since the 2-thienyl heterocycle is considered the bioisosteric equivalent of a phenyl ring, im considering that this analog of amphetamine would be commerciably viable and worthy of exploration.

^^I know a guy who made some N-Et amp and said that it was much 'calmer' than meth although it did have somewhat attenuated potency. Also, I dont recall anyone ever mentioning alpha-ethyl-PEA although I personally have not got an interest in either of these two compounds.


----------



## fastandbulbous

hugo24 said:
			
		

> Does anybody know N-Ethylamphetamin?Information appears extreme sparse on this one.



Oh yes! Many moons ago a friend & myself came into possession of 'a fair bit' of said compound and it is wasily on a par with amphetamine & methamphetamine in terms of abuse potential, CNS/locomotor stimulation etc. It's about on a par with amphetamine in terms of potency, but in terms of effect is a bit more like methamphetamine (probably due to octanol/water partition coefficient etc). It's longer lasting than amphetamine; more like meth, but doesn't seem to have anything like the potential of meth for driving people crazy etc.

Funnily, I remember reading at the time I had access to it that the S-isomer is metabolized (N-dealkylated to amphetamine) at a much slower rate than the R-isomer, so that might account for it's longer peroid of activity than amphetamine, but without doing to much to scramble the cognative processes like meth does.

It's one of those compounds I'd love to be able to come face to face with again, but sadly it was entered into the Misuse of Drugs Act about 14 years ago (Class C though!), so I don't think it's very likely



> Since the 2-thienyl heterocycle is considered the bioisosteric equivalent of a phenyl ring, im considering that this analog of amphetamine would be commerciably viable and worthy of exploration.



For some reason, replacing the phenyl group with a 2-thienyl group produces compounds that are fairly poor locomotor stimulants - I can't remember the refs., but if you look you'll find them as they were in one of the 'big' journals


----------



## yaesutom

^^  Also there's N-propylamphetamine, N-ethyl is schedule 1 in the U.S. but the propyl analog isn't (well its an analog but thats it).  A monkey on mars told me its weaker than amphetamine (i think 15mg N-propyl-A = 10mg amph.  something like that anyway) and similar to the above posted for N-ethyl, smoother and longer lasting.

I found something interesting, there is this amphetamine pro-drug called Fenoproporex, its N-2-cyanoethylamphetamine, and I believe its schedule IV in the U.S., also found out, that its being put in some (well one particular brand seems to come up in many searches..) "herbal" weight loss products imported from brazil and sold in the U.S. .  Easily found some of these places selling this herbal stuff by just googling fenoproporex.  Wonder if its got any action before its metabolised into amphetamine?  

Anyway I guess N-propyl-amphetamine would seem most interesting to get just 'cause its unscheduled.


----------



## Church

All I know is that if some of you chemists would get to making a euphoric, entactogenic amphetamine, one that doesn't necessarily cause the user to have epiphanies and psychospiritual revelations, I would pay top dollar for it.

Or, if there are still some chemists out there who aren't pussies about making drugs that are specifically controlled or illegal, would you please flood the markets with more MDA and less MDMA? Thank you.

MDA = the best recreational drug EVER!!!


----------



## hussness

Is there any general information available on how readily a certain type of acetyl group will get metabolized/hydrolized to the corresponding -OH?  This is for those of you with a background in pharmacokinetics.  I'm just curious because the acetyl group is ubiquitous in recreational substances.


----------



## Smyth

Yes, I have checked it out and there is not a lot of data on the subject, suggesting that it is simply a matter of common sense.

Bear in mind LAAM has an acetyl group so if the conditions are right, it can stay in-tact for quite some time. 
But even upon hydrolysis, is the free-hydroxy is still able to maintain the compounds high activity?

Since MAM makes up quite a big percentage of heroin that has been kept in storage for any length of time, im guessing that the phenol position is  suceptible to hydrolysis. Pka phenol = 10 vs. 16 for normal alcohol.

http://en.wikipedia.org/wiki/Psilocybin

Maybe this is a good place to consider what the relative effect of a phosphonate ester might have.

After that the order of ease of hydrolysis is primary>secondary>tertiary.

This is on the grounds of steric branching, whereas for the phenol it was an electronic effect.





http://en.wikipedia.org/wiki/3-quinuclidinyl_benzilate

See here in the above example how all the crazy steric bulk cuts out hydrolysis leading to a compound with a massively long half life even though esters are considered much more reactive than ethers. These bulked out phenyl groups are also present in LAAM. Also notice that although this is is a secondary alcohol, an ester is also composed of an acid portion. I know this is drifting off topic since your question was primarily concerned with the acetyl group. It does however show that steric bulking in both the alcohol and the acid elements can affect the kinetics of hydrolysis.

Classically we think of hydrolysis as an addition-elimination reaction and this mechanism is proven by radio-isotopic labelling experiments.

Since the reaction is bimolecular, steric crowding in the substrate around the reaction centre will block access of the water molecule (if acid catalysed) reducing the probability that a given trajectory will lead to a successful collision leading to formation of the reactive sp3 intermediate. 

Also since the mechanism involves rehybridization from sp2 to sp3, the activation energy will be dependent on whether steric eclipsing is reduced/ increased in the intermediate relative to the reactant. 

But then again this has its limitations. The free hydroxy in BZ gas would be difficult to esterify and even upon acetylation it would be readily hydrolyzed since it is energetically unstable. This is also a steric effect of there being excessive cramping, as oppose to lack of shielding.

With the two phenyl groups geminal to the tertiary hydroxy, im thinking that the reaction mechanism for hydrolysis might be elimination-addition, although this is just a theory.

I recommend u read this if u want further info: http://www.cem.msu.edu/~reusch/VirtualText/intro1.htm#contnt

While still using the original question as a spring board to look at other aspects of esters in drug molecules, see how it can be used as a time release mechanism in the following example:

http://en.wikipedia.org/wiki/Vanoxerine


----------



## hugo24

Ah,someone here had Ethamphetamin,who woulda have thought!
Just checked,yeah its also scheduled here.Hey wasn't that you who also tasted Ethcathinon (I think it lasted longer)?

Altough I read somewhere its a stimulant,the alpha-Ethyl-phenethylamin seems pretty inactive.T+0 20mg T+1h 20mg T+1.5h +40mg.feeling maybe something after it.T+2.5h +100mg.20' later I felt clearly the effects,heart beats faster (but the meter says only a miniscule increase 144/75 79).Maybe a peak at 4h,uneven heartbeat,152/86 64 the BP/PR values,stomach cramps,piloerection but no euphoria.Basically,just the physicals withouth any CNS effects.Taking more felt unsafe because of the heart irregularities.


----------



## fastandbulbous

^ Yeah, a friend who synthed some 1-phenyl-2-butylamine & it's N-methyl derivative said that they were rather disappointed with it in comparison with amphetamine. He did say though that the beta-keto analogues of alpha-ethyl PEA & the N-methyl compound were quite good CNS stimulants (he described the alpha-ethyl analogue of methcathinone as being almost as active as methcathinone).

Yeah, I've had N-ethylcathinone (the de-ethylated analogue of diethylpropion) a long time ago; it was pretty much on a par with methcathinone, but with less beta-adrenergic activity (pounding heart etc) as well - definitely a better CNS stimulant than diethylpropion


----------



## hugo24

That pretty fills the final holes on the close analogs of amp.
Again the bk's showing promise and a broader SAR profile.Pyrrolidino,para-fluoro,alpha dimethyl,valerophenon,n-propyl...


----------



## vecktor

*legal analogues*

if the purpose is to avoid the legal restrictions on the golden oldies then one might want to consider the prodrug derivatives of the various amines. Dihydronicotamide derivatives are very interesting as they are CNS specific, see the work of Bodor. In the mid 90's I identified other prodrug derivatives and routes to them not involving illegal precursors (in the UK) hint think isocyanates  but my research was curtailed by the aptly named criminal justice system.
regards V


----------



## snowblowjoe

r u seriously going to say MDA is a better stimulant than 4-mar or pure crystal/glass?


----------



## fastandbulbous

vecktor said:
			
		

> if the purpose is to avoid the legal restrictions on the golden oldies then one might want to consider the prodrug derivatives of the various amines. Dihydronicotamide derivatives are very interesting as they are CNS specific, see the work of Bodor. In the mid 90's I identified other prodrug derivatives and routes to them not involving illegal precursors (in the UK) hint think isocyanates  but my research was curtailed by the aptly named criminal justice system.
> regards V



Never really considered them as viable CNS stimulants in terms of psychomotor stims as they have quite prominant convulsant activity (eg nikethamide) & that's something that's def best avoided for any drug. 

Reuptake inhibitors seems to be the most promising area of research, it's just that there seems to be no hard & fast rule that distinguishes reuptake inhibitor drugs with very little stimulant effect from those with much more pronounced stimulant effects (see some of the WIN series vs cocaine)


----------



## vecktor

"Never really considered them as viable CNS stimulants in terms of psychomotor stims as they have quite prominant convulsant activity (eg nikethamide) & that's something that's def best avoided for any drug." 

I perhaps wasn't clear, I am refering to making amide derivative of say amphetamine, or methamphetamine for example, using dihydronicotinic acid see patent US5525727

Basically the scheme works as follows, the amide is absorbed and crossed the BBB, non polar so easily done. once in the brain the dihydronictoinamide portion is oxidised to the fully aromatic nicotinamide derivative this is unable to cross the BBB as it is highly polar. the nicotinamide portion is then rapidly cleaved by esterase giving nicotinc acid and our desired amine ( methamphetamine or whatever).  


As an aside this oxidation may be why LSD has extreme potency, LSD contains a dihydro pyridine ring, this can be oxidised to the pyridine which is highly polar and would not be able to cross back out of the brain through the BBB.


----------



## fastandbulbous

> As an aside this oxidation may be why LSD has extreme potency



No it's because LSD is essintially a planar molecule due to the conjugated double bonds associated with the aromatic nucleus. 5HT2a agonists display maximal affinity for the receptor when the molecule is planar (eg DOB-dragonfly)


----------



## mad_scientist

fastandbulbous said:
			
		

> Reuptake inhibitors seems to be the most promising area of research, it's just that there seems to be no hard & fast rule that distinguishes reuptake inhibitor drugs with very little stimulant effect from those with much more pronounced stimulant effects (see some of the WIN series vs cocaine)



In general, the abuse potential of dopamine reuptake inhibitors depends on how they affect the pattern of dopamine release and reuptake. Compounds that inhibit reuptake and also induce release of dopamine (such as methamphetamine or phenmetrazine), or compounds that inhibit reuptake but have no effect on release (such as cocaine, CFT, amineptine or methylphenidate) tend to be addictive drugs with potential for abuse in humans. On the other hand, compounds that inhibit reuptake but also inhibit release of dopamine (such as modafinil, mazindol, bupropion and vanoxerine) have mild stimulant effects and little abuse potential. 

Note that vanoxerine (GBR12909) binds to the dopamine transporter 300x more strongly than cocaine but has little stimulant effect because it induces a mild and long lasting increase in dopamine levels quite different from the short and intense dopamine peak produced by cocaine. A similar pattern is seen with the drugs affecting serotonin reuptake; SSRIs like prozac or citalopram produce a mild and long lasting increase in serotonin levels but have little abuse potential, wheras drugs like MDMA and 4-methylaminorex produce a sudden and intense release of serotonin (and dopamine) which produces much more intense euphoria.


----------



## Smyth

SSRIs work in a different way to MDMA. Although they are both thought to affect serotonin, they work in different mechanisms. Im not sure that duration of action can be directly linked to addiction as such, although it does have a part to play in determining the 'rush' factor.

MDMA also affects, to a lesser extent, dopamine and noradrenaline, whereas SSRIs are much more specific in their action no serotonin. 

Im thinking your theory is floored because that weould be like saying methadone has "little abuse potential" which clearly is of questionable validity.

The statement about vanorexine inhibiting dopamine release even though it is a potent DRI might be correct. I have seen this on Wikipedia. Quite simply I think people model the theory to fit the data. And when some new evidence emerges that doesnt fit the existing theory, a new one is postulated.

My view is that people take stimulants to get a surge in monoamines and that this is where the euphoria part comes from. Compounds that have a slow onset of action and are too 'lazy' fail int his regard. But this is not to say that compounds with a long duration of action or ones that are a bit slow off the starting blocks are not without their potential. I think that Indatraline may well have abuse potential which might be one of the reasons why it would not be a good candidate for cocaine addiction.


----------



## mepat1111

Smyth said:
			
		

> SSRIs work in a different way to MDMA. Although they are both thought to affect serotonin, they work in different mechanisms. Im not sure that duration of action can be directly linked to addiction as such, although it does have a part to play in determining the 'rush' factor.
> 
> MDMA also affects, to a lesser extent, dopamine and noradrenaline, whereas SSRIs are much more specific in their action no serotonin.
> 
> Im thinking your theory is floored because that weould be like saying methadone has "little abuse potential" which clearly is of questionable validity.


I may be wrong here as my knowledge here is limited, but I think he was trying to say that the abuse potential comes from the fact that MDMA induces the release of seratonin AS WELL AS inhibiting reuptake of seratonin. On the other hand, SSRIs only inhibite reuptake, meaning a gradual increase of seratonin levels, and less abuse potential. ie - the abuse potential comes from the combination of seratonin release and inhibiting the reuptake.

Also, would this be why it is so dangerous to take SSRIs with MDMA? As the seratonin released by MDMA would be already blocked for reuptake, increasing the effects greatly? I once met a guy who claimed he would sometimes take VERY small doses of MDMA while on anti-depressants (he had a script which he only used occasionally, apparently for phantom joint/muscle pain)  - he did not know what exactly was the name of the chemical and the brand name was useless to tell it, but I assume it was an SSRI - and it would increase the effects greatly.


----------



## Smyth

Yes but MDMA is similar in structure to dopamine and also adrenaline. My theory is that at least to some extent MDMA goes into the brain where the body confuses it with endogenous monoamines, ie a 'scrambling' effect is experienced by the user.

Whereas SSRIs have a more targeted role to play and binding to the presynaptic 5HTT and isnt getting treated like a monoamine.

Ie MDMA is a monoamine mimic, as is amphetamine abd a host of other simple two carbon chain amines.

Although the therapeutic lag of antidepressants can be as long as several weeks, it actually starts inhibting the reuptake of 5HT as soon as the tablet is swallowed. 

I personally actually can feel a strong effect from SSRIs even after one tablet. It's just that I dont think the mechanism of causing a sole increase in 5HT availability is someone that would make me happy. Combining a 5HTT reuptake inhibitor with a reliably self-administered doapminergic can even serve to attenuate drug seeking behavior according to some recent journals (last decade).

Plus it is not dangerous to combine an SSRI with MDMA. MDMA causes the 5HTT pump to work in reverse flooding the synpatic cleft with serotonin (this is according to scientific research not my own opinion). whereas 5HTT blockers are gonna stop transport in both directions presumably thereby 'blocking' the effect of MDMA.


----------



## mad_scientist

SSRIs block the reuptake transporter and so serotonin levels in the synapse rise, but this then activates autoinhibitory 5HT1B/1D receptors which limit further serotonin release. This, coupled with the long half-life of the SSRI in the body produces a subtle but long-lasting increase in serotonin.

MDMA on the other hand triggers the standard non-selective monoamine release of amphetamines in general, releasing increased amounts of dopamine, noradrenaline and serotonin by inducing vesicle trafficing. However it also reverses the 5HTT serotonin transporter and so releases serotonin by a second seperate mechanism, hence why MDMA releases much larger amounts of serotonin than most amphetamines. The half-life of MDMA is however fairly short, also it uses up most of the pool of serotonin in the neuron quite quickly and so its action tends to be self-limiting unless there is extra 5HTP avaliable to make fresh serotonin from. 

Pretreatment with SSRIs blocks the effects of MDMA by preventing it from entering the neuron through the 5HTT (and hence stopping the MDMA from reaching either of its two targets inside the cell). However if you take an SSRI just as the MDMA is starting to wear off, it can indeed block the reuptake of the serotonin the MDMA has dumped in your brain and make the serotonin peak last much longer - unfortunately this is not generally pleasent though as the serotonin receptors start to get desensitised, so the positive effects from the MDMA wear off and just leaves a hot, sweaty, nauseous, anorexic too-much serotonin feeling, which can last for days. So I guess there could be some risk of serotonin syndrome etc if SSRIs and MDMA were combined in a high dose, especially if 5HTP were taken as well.


----------



## mad_scientist

Smyth said:
			
		

> Im not sure that duration of action can be directly linked to addiction as such, although it does have a part to play in determining the 'rush' factor.
> 
> Im thinking your theory is floored because that weould be like saying methadone has "little abuse potential" which clearly is of questionable validity.
> 
> My view is that people take stimulants to get a surge in monoamines and that this is where the euphoria part comes from. Compounds that have a slow onset of action and are too 'lazy' fail in this regard. But this is not to say that compounds with a long duration of action or ones that are a bit slow off the starting blocks are not without their potential. I think that Indatraline may well have abuse potential which might be one of the reasons why it would not be a good candidate for cocaine addiction.



In general, drugs with fast onset and short duration of action have higher abuse potential in the short term, (ie abuse potential of fentanyl>heroin>methadone) but this does not remain true when the drugs are used for a long period of time, indeed I've been told that methadone maintenance can be even more difficult to give up than heroin, once the person has been on the methadone program for a long time. However the theory would predict that fentanyl will be easier to get hooked on in the first place.

I'm not sure how generally this holds true in real-world situations. Personally I found methamphetamine to be much more addictive than cocaine, even though it has much longer duration of action, but I think speed of onset and how intense the initial "rush" from the dopamine peak feels has a lot to do with how addictive a particular substance is, hence why different routes of administration also often tend to show varying abuse potential (IV>IM>SC>smoking>snorting>eating), even where the same drug is being used.


----------



## BilZ0r

> Pretreatment with SSRIs blocks the effects of MDMA by preventing it from entering the neuron through the 5HTT (and hence stopping the MDMA from reaching either of its two targets inside the cell). However if you take an SSRI just as the MDMA is starting to wear off, it can indeed block the reuptake of the serotonin the MDMA has dumped in your brain and make the serotonin peak last much longer



What are the two targets of MDMA inside the cell?

SSRI can potentiate MDMA? Got any citations for that? The half-life of 5-HT clerance is like 10-100 seconds. If you slowed clerance and release at the same time, you're boost should only last for a couple of minutes.


----------



## mad_scientist

The two targets of MDMA are the 5HTT transporter on the cell surface and the VMAT-2 transporter on the surface of storage vesicles. I'm not sure that the exact binding domain on either protein has been established.

Taking SSRIs when an MDMA pill is wearing off does indeed produce hot flushes, anorexia and insomnia for 2-3 days afterwards which would presumably be attributed to excess serotonin levels, but I'm not sure that this has been confirmed by any formal research. Although admittedly these symptoms could be from other causes than serotonin, a serotonergic cause would seem likely when they are produced by co-administration of two drugs that are known to be primarily serotonergic in action. Certainly there would seem to be some interaction between the two drugs that is producing a long-lasting elevation of serotonin levels, regardless of the mechanism.

Under what circumstances is the half-life of 5HT clearance 10-100 seconds? Normal (drug-free) conditions with a functioning 5HTT reuptake transporter to suck it back up out of the synapse? I would imagine the half-life is longer when the only route of clearance is passive diffusion and degradation by MAO (which is also partially inhibited due to the slight MAOI effect of the MDMA). Or maybe the SSRI and MDMA just have some pharmacokinetic interaction which extends the period that serotonin is released for.


----------



## hugo24

IPAMP,N-Isopropylamphetamin.Appears like a hole.I guess if ethyl and propyl are active,the isopropyl is active as well.Judging by this paper I guess a 40mg dose:

"*Deuterium isotope effects in the metabolism of N-alkyl-substituted amphetamines in man. *    Vree, T. B.; Gorgels, J. P. M. C.; Muskens, A. Th. J. M.; Van Rossum, J. M.    Dep. Pharmacol.,  Cathol. Univ. Nijmegen,  Nijmegen,  Neth.    Clinica Chimica Acta  (1971),  34(2),  333-44.  CODEN: CCATAR  ISSN: 0009-8981.  Journal  written in English.    CAN 77:106    AN 1972:400106    CAPLUS  

Abstract

Comparison of the excretion rates of amphetamine (I) [2706-50-5], methylamphetamine [4298-16-2], isopropylamphetamine [33286-26-9], and dimethylamphetamine [33286-27-0] with the respective deuterated compds. by humans given oral doses of 7-40 mg indicated that the tertiary hydrogen was involved in the enzymic N-alkylation and deamination of these compds.  "


Not much known about the t-Butyl !?


----------



## fastandbulbous

The N-isopropyl compound has more beta-adrenergic activity (pounding heart etc) so isn't the first choice when it comes to N-alkylated amphetamines.

Personally, I'd go for N-allylamphetamine as it's likely to be very similar to N-propylamphetamine


----------



## 125mg

*4-Methylaminorex*



			
				Riemann Zeta said:
			
		

> Phenmetrazine is too hard to synthesize.  It requires nor-ephedrine, which was banned in 2000.  Same goes for 4-methylaminorex (4-MAX), which is why both are as rare as it gets in the drug world.



Since when did 4-methylaminorex become hard to synthesize?
Oh no, they banned some pills, we're screwed.. you must be kidding right?

Might I introduce you to the wonderful and exciting world of clandestine chemistry?
No pills, just lots of chems.

The notion that 4-MAR is a difficult synth compared with other drugs is a complete myth, quite a common one too, the same ill-advised statements being repeated over and over again all over these threads by people who actually have no clue what they are talking about. 

The 4-MAR synth is a piece of cake. Noone uses highly toxic cyanogen bromide to make that anymore, anyone who thinks otherwise needs to get with the times or just has no clue, except they have proven themselves able, without even leaving their chair, to use an internet search engine to dredge up Eleusis's dated 4-MAR procedure. As for said procedure, every underground chemist knows isn't worth a dime btw. Its outdated, dangerous and of no use to anyone.
Printing off such internet "recipes" is hardly what one would call real research, the valuable chemical procedures are to be found in a good library, not in Erowid's Vaults.
Instead of cyanogen bromide, relatively nontoxic and easily made potassium cyanate is now used as part of a simple one pot synthesis (aka the famous 4-MAR Shake'n Bake synthesis) with very high yields. 
In recent years underground chemists have developed new procedures, quite unlike most of the aforementioned obsolete & dangerous 4-MAR recipes floating around the web. Things have come along way in the last 10 years, clandestine chemists have made significant breakthoughs and I assure you the best procedures, NEVER get put on the web since doing so would mean swift controls placed on the precursors. 
The main precursor for 4-MAR is still PPA (phenylpropanolamine), though synthesizing it is NOT exactly a great endeavour, and it makes absolutely no difference that PPA has been removed from cold remedies by the FDA !! That would only affect the reject good-for-nothing pill cooks, and is hardly going to affect the actual clandestine chemists who are the ones, aka "Bees" , doing all the work. The 4-MAR synth is a snap.

PPA can be made extremely easily from just benzaldehyde and l-alanine with 15% yield of PPA (akabori reaction), though low yielding it is a straight forward reaction and easy to do.
The best process that is used to synthesize PPA is almost exactly the same as that used to produce phenyl-2-nitropropene (phenyl-2-propanone precursor) except a slight variation (adding NaOH) in 2 simple process stages yields the PPA with 70% yields. So you can't say PPA is inaccessible !!!!!!!!!!! 

The aforementioned phenyl-2-propanone precursor (phenyl-2-nitropropene) is produced by a reaction known as the "Knoevenagel Condensation" , which is the preferred route to large scale phenyl-2-propanone (#1 Meth & Amphetamine precursor). Especially for the big labs !

Which means of course.....: that if you are producing Meth, you are statistically most likely to be producing it from phenyl-2-propanone (& methylamine), which was probably produced via the Knoevenegal condensation (using benzaldehyde & nitroethane), which rather conveniently, is precisely the reaction thats extremely EASILY adapted to yield phenylpropanolamine (in 2 stages) instead of the phenyl-2-nitropropene !! The PPA variation is actually easier and requires cheaper chemicals than the phenyl-2-nitropropene route used for meth !
 If you wont listen to me, go research the chemistry for yourself. Check out the PPA & ephedrine synth on Rhodium's page to get you started. 

So, basically if they can make meth they can probably make PPA too, and without all the hassle of converting the phenyl-2-nitropropene to phenyl-2-propanone, or playing with listed methylamine with subsequent reduction of the schiff's base to form meth, etc etc etc
The workup from PPA to 4-MAR is so simple its stupid, literally. If you've acquired PPA, then you have 4-MAR. Compared to the work involved in producing the PPA, the conversion step(s) to 4-MAR (by comparison) requires neglible effort.

4-methylaminorex (freebase or salt) is actually easier, cheaper & quicker to produce than crystal methamphetamine. 

The problem is, there just aren't large scale labs producing it since they are busy 24/7 producing meth.

Any mention of the 4-MAR synth being too difficult is pure fantasy, and I've read the same lie in no fewer than 10 separate posts just in the last hour while researching 4-MAR... 
Such misinformation is rife. 
Its all too tempting for a novice chemist to simply look at the oxazoline ring (without getting off his lazy butt and doing some actual research) within the 4-MAR molecule and talk all day about how difficult it is to produce due to the complexity of having to painstakingly "construct" the oxazoline ring, nonsense - its simple.
PPA & potassium cyanate (simple 2 hr reflux), followed by simple acid hydrolysis and Voila ! PPA to 4-methylaminorex, just like that. From start to finish, 4 hrs and can be scaled up to any size. 
This ain't rocket science, so why all the confusion? 
These procedures ARE actually on the web, if in any doubt go check them out for yourself. 
The hive files are a good place to start.


 4-MAR isn't hitting the streets in bulk for one simple reason:  MONEY.
Nothing to do with the chemistry. Meth is what the junkies want, meth is what they shall have. 

As for the most promising candidate for the stimulant of the future?
 If all those presently operating the clandestine labs were to suddenly decide they can make more money from producing 4-MAR instead,  they could be turning out the same weekly tonnage of 4-MAR within a short while if they really wanted to. 
4-MAR is one hell of a drug, far more potent than meth, most would agree that overall its simply a superior drug, and it seems to be growing in popularity all the time.

I'm guessing that 4-MAR is here to stay   


MODS: I've made every attempt to limit chem synthesis reference(s) as much as possible, synths mentioned are simply there to help clarify the logic in the point I'm trying to present. Plz feel free to edit/delete/ if/where necessary.


----------



## fishinabottle

For a matter of fact you have no clue. Sorry. Thats not so easy and without pointing out all whats wrong what would just be about everything lets just say this:
The reactions for PPA mentioned produce ALL a mixture of razemic norephedrine and norpseudoephedrine. The convient "shake and bake" synthesis calls for PPA which is l-norephedrine in this context. 
And?
Says that only a quarter of what you put in will get 4-MAR so you are lucky.

Not so good.

As told, you have no clue, sorry.


----------



## 125mg

fishinabottle said:
			
		

> For a matter of fact you have no clue. Sorry. Thats not so easy and without pointing out all whats wrong what would just be about everything lets just say this:
> The reactions for PPA mentioned produce ALL a mixture of razemic norephedrine and norpseudoephedrine. The convient "shake and bake" synthesis calls for PPA which is l-norephedrine in this context.
> And?
> Says that only a quarter of what you put in will get 4-MAR so you are lucky.
> 
> Not so good.
> 
> As told, you have no clue, sorry.




IIRC, the 4-MAR shake'n bake procedure hasn't been updated in years, and the said posts discussing the norephedrine isomerism within that thread were based on theory alone. I also believe that they were aiming to produce  trans-4-MAR, however this isn't necessary since all resulting 4-MAR isomers are active.
The main point in my original post is the large scale synth of PPA, there are many ways to convert the PPA into 4-MAR, the shake'n bake was just one convenient well known EXAMPLE. The conversion step still remains a low level effort regardless of any isomers that were to prove incompatible with the shake'n bake cyanate one-pot synth.. 

Base your judgement on actual trials instead of mere anecdotal conjecture.

The isomerism was a topic of some discussion, but limited to theory. 
The yield isn't 25% if using racemic norephedrine.

This isn't theory (sense the tone..), and reportedly yields over 70%. If you think otherwise, tell that to the chemists making such weird claims.

 Also, there are many variations of the so called shake'n bake, the shake'n bake is notable since its a one pot synth, handy for the individual cook. Whether it's a one pot synth or not is irrelevant as far as large scale drug manufacturing is concerned. Obviously any large scale manufacturing isn't going to be a "one pot synth". The hive 4-MAR cyanate thread was given as a web reference simply to corroborate the general method I was referring to.

For arguments sake, even if the racemic feed where to reduce yields, then the procedure would simply be adjusted accordingly and ultimately it wouldn't be a one pot synth anymore, so what's your point? No point at all, you're just being a smartass and thats why I can't be bothered.
I'm not prepared to waste my  time debating whether or not something works since its highly unlikely the scope of discussion will ever progress beyone the theory and into the experimental realm. 

Besides, if the dialogue I've seen so far is any indication of whats yet to come, then I doubt I'll be hanging around. : )
I've every confidence in the accuracy of the information given, and see nothing to gain by arguing with complete strangers.
Peace.


----------



## Dr. Beat

mad_scientist said:
			
		

> In general, the abuse potential of dopamine reuptake inhibitors depends on how they affect the pattern of dopamine release and reuptake. Compounds that inhibit reuptake and also induce release of dopamine (such as methamphetamine or phenmetrazine), or compounds that inhibit reuptake but have no effect on release (such as cocaine, CFT, amineptine or methylphenidate) tend to be addictive drugs with potential for abuse in humans. On the other hand, compounds that inhibit reuptake but also inhibit release of dopamine (such as modafinil, mazindol, bupropion and vanoxerine) have mild stimulant effects and little abuse potential.



i thought the DARI's were the same mechanism : i thought it was that modafinil and bupropion are weak but long acting DARI's.

and i thought that why cocaine is more addictive than methylphetnidate is because it is a SSRI that causes even more dopamine release compared to 'straight' DARIs


----------



## fishinabottle

> The isomerism was a topic of some discussion, but limited to theory.
> The yield isn't 25% if using racemic norephedrine.
> 
> This isn't theory (sense the tone..), and reportedly yields over 70%. If you think otherwise, tell that to the chemists making such weird claims.


 For the potassium cyanate route one needs l-norephedrine - and thats the PPA used in pills in the USA.

Nobody doubts that making 4-MAR from extracted PPA pills works in good yields.

Everything told about the easiness of PPA production is just not really true, for the procedures are not so simple and the result of the presented pathways is always a racemic mixture from which only 1/4th is useable. And thats that. Except you want to work with cyanogen bromide then it would be 50%.


----------



## 125mg

fishinabottle said:
			
		

> For the potassium cyanate route one needs l-norephedrine - and thats the PPA used in pills in the USA.
> 
> Nobody doubts that making 4-MAR from extracted PPA pills works in good yields.
> 
> Everything told about the easiness of PPA production is just not really true, for the procedures are not so simple and the result of the presented pathways is always a racemic mixture from which only 1/4th is useable.



 For arguments sake, lets just say you only want to use one specific isomer only such as with trans-4-MAR, thats not a problem no matter which isomer is desired - so why pretend like it is? Amino alcohols are versatile, useful compounds that have more uses in drug chemistry, to even bother to list. 

There is no such thing as "unusable" PPA, for instance its very easily converted to P2P with high yields, via a simple acid hydrolysis using ZnCl2 as catalyst (iirc Rhodium mentions this as well). And before you mention it, I can assure you that this reaction is not stereospecific, it gets turned into ketone with around 80% efficiency. 

That P2P would then go on to produce the meth with no reduction in overall yields since the PPA to P2P conversion step is just as efficient as the phenyl-2-nitropropene to P2P conversion usually used in meth synthesis. All large scale drug labs currently producing P2P via the phenylnitropropene could easily go the PPA route intead, using the desired isomer and turning the remainder into P2P and then onto meth i.e. business as usual.

Alternatively the "unusable" isomers could simply be REDUCED straight to amphetamine via any number of routes (again, non-stereospecific), well within the capacity of large scale drug labs. 
So basically fishinabottle, even in the WORSE case scenario that you are suggesting, the "disaster" that lies ahead is merely a hybrid lab producing both 4-MAR & meth, simple and easy.


----------



## fastandbulbous

> I'm not prepared to waste my time debating whether or not something works since its highly unlikely the scope of discussion will ever progress beyone the theory and into the experimental realm.



I know it fuckin' will not - did you read the bit about no discussion of synthesis? There are other sites that deal with drug synthesis, but Bluelight isn't one of them.

Anyone attempting to continue discussing synthesis will be dealt with...


----------



## hugo24

*MOPPP and PPP*

Hmm,seems other propiophenons are known,haven't read anything here!?

"*Studies on the metabolism of the new pyrrolidinopropiophenone designer drugs PPP and MOPPP. *    Springer, Dietmar; Peters, Frank T.; Fritschi, Giselher; Maurer, Hans H.    Hessisches Landeskriminalamt,  Wiesbaden,  Germany.  Editor(s): Pragst, Fritz; Aderjan, Rolf.    GTFCh-Symposium: Toxikologische Aspekte der Sterbehilfe--Neue Drogen: Chemische, Analytische und Toxikologische Aspekte, Beitraege zum Symposium der Gesellschaft fuer Toxikologische und Forensische Chemie, 12th, Mosbach, Germany, Apr. 26-28, 2001  (2001),  Meeting Date 2001,     156-161.  Publisher: Verlag Dr. Dieter Helm,  Heppenheim, Germany  CODEN: 69CPGU  Conference  written in English.    CAN 138:19085    AN 2002:394040    CAPLUS  

Abstract

a-Pyrrolidinopropiophenone (PPP) and 4'-methoxy-a-pyrrolidinopropiophenone (MOPPP), new designer drugs of the a-pyrrolidinopropiophenone type, have appeared on the illicit drug market.  In the meantime, PPP has been listed in the German Act of Controlled Substances.  This work used gas chromatog.-mass spectrometry to study the urinary metabolites of PPP and MOPPP after administration to rats.  PPP was predominantly metabolized by hydroxylation of the pyrrolidine ring, followed by dehydrogenation to the corresponding lactam or by hydroxylation of the arom. ring.  MOPPP was almost completely metabolized, predominantly by O-demethylation and/or by hydroxylation of the pyrrolidine ring, followed by dehydrogenation to the corresponding lactam, and to a minor extent by hydroxylation of the arom. ring.  The phenolic OH groups were partly conjugated.  

--------------------------------------------------------------------------------------------------

*Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types. A synopsis. *    Maurer, Hans H.; Kraemer, Thomas; Springer, Dietmar; Staack, Roland F.    Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology,  University of Saarland,  Homburg,  Germany.    Therapeutic Drug Monitoring  (2004),  26(2),  127-131.  Publisher: Lippincott Williams & Wilkins,  CODEN: TDMODV  ISSN: 0163-4356.  Journal; General Review  written in English.    CAN 141:133389    AN 2004:397772    CAPLUS  

Abstract

A review.  Designer drugs of the amphetamine type (eg, MDMA, MDEA, MDA), of the new benzyl or Ph piperazine type (eg, BZP, MDBP, mCPP, TFMPP, MeOPP), or of the pyrrolidinophenone type (eg, PPP, MOPPP, MDPPP, MPPP, MPHP) have gained popularity and notoriety as rave drugs.  These drugs produce feelings of euphoria and energy and a desire to socialize.  Although in the corresponding drug scene designer drugs have the reputation of being safe, studies in rats and primates in combination with human epidemiol. investigations indicate potential risks to humans.  Thus, a variety of adverse effects were assocd. with the use/abuse of this class of drugs in humans, including a life-threatening serotonin syndrome, hepatotoxicity, neurotoxicity, and psychopathol.  Metabolites were suspected to contribute to some of the toxic effects.  Therefore, knowledge of the metab. is a prerequisite for toxicol. risk assessment.  The metabolic pathways, the involvement of cytochrome P 450 isoenzymes in the main pathways, and their roles in hepatic clearance are described for designer drugs of different groups.  In summary, polymorphically expressed CYP2D6 was the major enzyme catalyzing the major metabolic steps of the studied piperazine- and pyrrolidinophenone-derived designer drugs.  However, it cannot be concluded at the moment whether this genetic polymorphism is of clin. relevance.


----------



## nuke

Do you have the full text of either of those articles, hugo24?


----------



## fastandbulbous

PPP is just the ring amine version of diethylpropion (the diethylamino group being condensed into a pyrrolodino ring) and is fairly similar in effect to the aforementioned diethylpropion (chalkies, tombstones etc).


----------



## glenn2244

*Negatives re methamphetamines*

I have admired these since Abbott Labs created the perfect drug: Desbutol.  Ten Mg Methamphetamine Hcl with an attached Nembutol to make the experience either more mellow or to use at bed time.  I see it as a crime that these types of drugs are becoming impossible to find in any form. Is there any hope of some revival of this drug being available?


----------



## hussness

No.  Precisely because they're fun.  There's already a thread on this, by the way.


----------



## mepat1111

Of course pure Amphetamine exists, what do you think Adderall and Dexedrine are? This is hardly the correct thread for asking that sort of thing...


----------



## johanneschimpo

^ I think s/he meant "on the street". like a sack, not pills.
and there's no real answer to that question, as far as I know.


----------



## mepat1111

It depends who you know and where you come from as to whether you can find it these days. But yes it does still exist.


----------



## Coolio

You can't find amphetamine in the USA, Canada, or Australia for a host of precursor supply, market demand, user preference, etc. reasons. You can't find methamphetamine in Europe for the same reasons.

P.S. if whoever reads this is an example of how I'm wrong, realize that you're in a tiny minority. I think getting clandestinely synthesized amphetamine outside of Europe is as easy as finding 4-methylaminorex.


----------



## hugo24

Someone is looking closer into the class,note the year.To give an idea of dose,
"Pyrovalerone-HCl (I-HCl) [1147-62-2] in daily oral doses of 40-160 mg decreased the symptoms related to chronic fatigue in symptomatic human volunteers.  "

*1-(4-Methylphenyl)-2-pyrrolidin-1-ylpentan-1-one (Pyrovalerone) Analogs: A Promising Class of Monoamine Uptake Inhibitors. *    Meltzer, Peter C.; Butler, David; Deschamps, Jeffrey R.; Madras, Bertha K.    Organix Inc.,  Woburn,  MA,  USA.    Journal of Medicinal Chemistry  (2006),  49(4),  1420-1432.  Publisher: American Chemical Society,  CODEN: JMCMAR  ISSN: 0022-2623.  Journal  written in English.    CAN 144:331200    AN 2006:83142    CAPLUS  

Abstract

Dopamine, serotonin, and norepinephrine are essential for neurotransmission in the mammalian system.  These three neurotransmitters have been the focus of considerable research because the modulation of their prodn. and their interaction at monoamine receptors has profound effects upon a multitude of pharmacol. outcomes.  Our interest has focused on neurotransmitter reuptake mechanisms in a search for medications for cocaine abuse.  Herein we describe the synthesis and biol. evaluation of an array of 2-aminopentanophenones.  This array has yielded selective inhibitors of the dopamine and norepinephrine transporters with little effect upon serotonin trafficking.  A subset of compds. had no significant affinity at 5HT1A, 5HT1B, 5HT1C, D1, D2, or D3 receptors.  The lead compd., racemic 1-(4-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one, was resolved into its enantiomers and the S isomer was found to be the most biol. active enantiomer.  Among the most potent of these DAT/NET selective compds. are the 1-(3,4-dichlorophenyl)- and the 1-naphthyl-2-pyrrolidin-1-ylpentan-1-one analogs.


----------



## Smyth

C6H6 said:
			
		

> There are many very potent dopamine/monoamine reuptake inhibitors which have no recreational value whatsoever. Mazindole and bupropion are good examples. And just because a compound has a stimulant effect in mice or rats doesn't mean it has recreational value. I've made quite a few compounds which are stimulants for rodents but are useless for humans. Finding good new stimulants isn't as simple as it might seem.


I wonder what compounds he made? Bupropion is a bad example btw because it is weak. 

Mazindol is potent though. However I also understand that it does have some positive effects even though it is not as strongly craved after as some of the more classical stimulants.


----------



## nuke

hugo24 said:
			
		

> Someone is looking closer into the class,note the year.To give an idea of dose,
> "Pyrovalerone-HCl (I-HCl) [1147-62-2] in daily oral doses of 40-160 mg decreased the symptoms related to chronic fatigue in symptomatic human volunteers.  "
> 
> *1-(4-Methylphenyl)-2-pyrrolidin-1-ylpentan-1-one (Pyrovalerone) Analogs: A Promising Class of Monoamine Uptake Inhibitors. *    Meltzer, Peter C.; Butler, David; Deschamps, Jeffrey R.; Madras, Bertha K.    Organix Inc.,  Woburn,  MA,  USA.    Journal of Medicinal Chemistry  (2006),  49(4),  1420-1432.  Publisher: American Chemical Society,  CODEN: JMCMAR  ISSN: 0022-2623.  Journal  written in English.    CAN 144:331200    AN 2006:83142



interesting.  this drug is already cheduled in canada (scheduled in 2003 with zolpidem and a few others)

has anyone thought about a methylenedioxy aminorex?  seems like it'd be a good target.


----------



## /navarone/

i obviously know less than u guys but after reading pikhail i saw this veeeeery intrigueing substance. 
I dont remember the name of it but it was a phenyethylamine and it had a few deuterium atoms attached to it instead of hydrogens.

Do u think that the introduction of deuterium or/and nitrogen isotopes could potentiate some of todays synthetic drugs, leading to a 'new' point of view on drugs?

deuterium is a rare isotope but it can easely be extracted from common water as heavy water (D2O).


----------



## hussness

I think isotopes of less abundance exhibit the same chemical reactivity, so I doubt it would potentiate anything.  But they are useful for mechanistic studies.


----------



## Helios.

Sennokot


----------



## Helios.

*Long Shot, Perhaps, But...*

Here Goes...Phenylisopropylpiperidine.
{As is (C6H5)CH2CH(CH3)piperidine.}


----------



## mepat1111

Sennokot was a laxative last time I checked.


----------



## Helios.

*Another Winner.*

Sennokot is a laxative because ppl were discussion opiods under "Stimulants of the Future."  Get it?

And while we're back on topic ("Stimulants of the Future"), may I also mention
Phenyl-ch2-(alpha)piperidine.  Namely, des-(-COOMe)methylphenidate.


----------



## mepat1111

Well I couldn't find any articles on google for ANY of the compounds you've mentioned in any of your posts over the last few hours, want to quote some sources with some info on them?


----------



## hugo24

The "piperidylamphetamin" is known,read some abstracts about it being a stimulant.But I would go for the pyrrolidino analog.

The des-COOMe phenidat looks interesting-has someone looked into it closer yet?I think it was mentioned in a thread before.


----------



## Helios.

The sneat thing about this latter one [phenyl-ch2-(alpha)piperidine] is that it appears to be almost inert to bodily metabolism other than possibly 
4-hydroxylation.  And then there are the 3-chloro and the 3,4-methylenedioxy derivatives.


----------



## Helios.

And the 3,4-dimethoxy and the 3,4-dichloro and the 4-methoxy and the 
4-chloro and the 3-ethoxy and the 3-methoxy and the 4-ethoxy and the 
4-propoxy and the 4-(n)-pentyl-2,5-dimethoxy derivatives....


----------



## nuke

what about 2-amino-tetralin and 2-amino-1,2-dihydronaphtalene?  anyone tried?  it seems like there's potential for the latter to have serotonin activity with some substitution, too


----------



## hussness

hugo24 said:
			
		

> The "piperidylamphetamin" is known,read some abstracts about it being a stimulant.But I would go for the pyrrolidino analog.
> 
> The des-COOMe phenidat looks interesting-has someone looked into it closer yet?I think it was mentioned in a thread before.



Do you have any references for that?  I couldn't find anything.


----------



## Helios.

No, I thought of them (that is, the PMAPs) myself.

PhenylMethyleneAlphaPiperidenes.

I got the idea from Ritalin/methylphenidate.


----------



## el_mago

hiyall, 

saw one of you speculating about 2-amino-tetralin and feel obligated to post 
a warning story i heard from dear friend of mine:

it's absolutely vile stuff and should be avoided like the plague.  yes the 
rat studies look good, but no, humans are not rats and the data can not be 
easily extrapolated.

my friends experimentation with this compound 8 years ago gave him a big life 
lesson and he's lucky to still be here. now he's not so eager to test never 
before been tried compounds.  it's a fine line and i advise extreme caution
when working something up. some of my friends mishap was inexperienced
pilot error, after several days of ramping up slowly on seperate experiments,
he got impatient and boosted a double dose 3 hours after taking the first dose
(was getting slight effect from first dose and figured 3 hours was enough time
 and should have peaked), then it all hit like a frieght train. very dysphoric,
 nothing like amph, sedated, sick and wierd feeling, total agony. continued
 accent and passed out completely unconscious at 4-5 hour point and came to
 consciousness about 3-4 hours later completely surprized that he was still 
alive.  he was able to call friend for help at that point and seemed like was 
leaving system slowly and was going to be OK. decided not to go to hospital to
 avoid explaining situation and potential police inquiry. 

friend took him to her
 house and crashed in bed feeling sick and nauseous. some 6 hours later he
 woke up middle of the night to go pee and on way into the bathroom passed 
out completely (maybe due to low blood pressure) and did a face plant into
shower door slicing his face and severely breaking his nose. blood everywhere,
friend wakes up and sees him in pool of blood on the floor barely able to 
maintain consciousness.  was able to get bleeding stopped and then passed 
out in bed from pain. awoke next morning in intense pain and found his nose 
was on the wrong side of his face. required surgury, long recovery, etc. truly a 
nightmare. 

abandon hope all yee who enter here

sincerely,

purple heart


----------



## nuke

Well, thanks for the anecdote.  That's interesting that it's so acutely toxic though; maybe mao inhibition?


----------



## Helios.

Interesting, now tell us about 3,4-di-Chloro-PMaP and PMaP.


----------



## Dondante

1-Naphthalen-2-yl-2-pyrrolidin-1-yl-pentan-1-one looks interesting.  Might be a little too good at binding all those monoamine transporters.  

Also, does it make sense to assume that the 3,4-methylenedioxy analogue (MDPV) would be similar to the 3,4-dihydroxy shown in the paper Nuke posted?  Looks like a farily similar profile to methylphenidate except 5x as potent (3-5x as potent on dopamine reuptake and DAT; 6-8x as potent on norepinephrine reuptake and NET; no SERT inhibition).   Makes sense from initial reports suggesting 5 mg MDPV.

It's odd that the naphthyl analogue affects SERT and serotonin reuptake so strongly when most of the others have a negligible effect.  Hmmm ... how about adding that naphthyl to some phenethylamines?  1-Naphthalen-2-aminopropane?  Any thoughts?


----------



## Smyth

2C-G5 looks cool. The thing is, I thought the general code of conduct is that people try and discriminate _against_ serotonin and not in favor of it. I may be wrong though. A similar result was also uncovered when dealing with methylnaphylate (c.f. methylphenidate) isomers. <- That is, the buck of the naphthyl compounds toward 5-HT did not fit-in with the general trend and was out of character.


> 1-Naphthalen-2-aminopropane? Any thoughts?


Im sure people have tried it only it wasnt very popular and has subsequently never established any sort of reputation. Still, i'd like to hear any accounts on this compound also - even negative ones, just to try and find out what the crack is wit this shit.


----------



## Dondante

2C-G-N is 1,4-dimethoxynaphthyl-2-ethylamine, but Shulgin never brougt it up to active levels.  (Edit: oops, I guess he did)  I think the aromatic naphthyl would make it significantly different from 2C-G-5 or 2C-G-3 just because of those free electrons.  Sorry, I'm getting off topic since these are almost certainly not going to be "stimulants of the future" in the meaning of this thread.  

I do wonder what Shulgin's 2C-G-N would be like, but I'd almost rather take off the 1,4-dimethoxy and see what happens.  One can only wonder.



			
				Smyth said:
			
		

> 2C-G5 looks cool. The thing is, I thought the general code of conduct is that people try and discriminate against serotonin and not in favor of it. I may be wrong though. A similar result was also uncovered when dealing with methylnaphylate (c.f. methylphenidate) isomers. <- That is, the buck of the naphthyl compounds toward 5-HT did not fit-in with the general trend and was out of character.



I agree, short, reversible SERT inhibitors must not be too good in treating ADHD or they wouldn't have gone for methylphenidate.  I'm not sure exactly why.  The 3,4-dihydroxy analogue seems to be a potentially good candidate for ADHD treatment, especially if the half life is slightly longer.  The 3,4-dichloro might be interesting too.  It has a preference for DAT and NET, but also affects SERT, only a little more weakly.  

Anyone know why they tried to avoid the serotonin system with the discovery of methylphenidate and its analogues?


----------



## Helios.

Smyth is right about SERT being non-reinforcing, but moth ball based medicine is not where it's headed.


----------



## Smyth

I meant 2cg, I just havent consulted alot of pihkal recently. What im saying is that most of the ring substituted methylphenidate analogs are intrinsically psychostimulant in nature with little 5-HT affinity. The same holds for derivatives of pyrovalerone. 3,4-dichloro is the most potent DAT inhibitor in the series but its still follows the trend IC50 DAT << 5HT. It's the b-napthyl moiety that 'bucks the trend'. Im calling it methylnapthidate for slang but its by no means official. If you want ref's then send me a pm with youe email addy and i'll forward a couple of relevent articles to evidence it.


----------



## Dondante

Helios. said:
			
		

> Smyth is right about SERT being non-reinforcing, but moth ball based medicine is not where it's headed.



I'm sorry man, but you really need to stop making worthless posts, some of which are blatantly wrong yet somehow you seem to state them with such confidence.  

Anyway, I will preface this by saying that I am not the all-knowing specialist that Helios is, however, why would MDMA be so popular if SERT inhibition added nothing positive to the experience?  MDMA is a potent inhibitor of SERT and DAT.  Also, cocaine goes for all three transporters.  Actually, I found an article supporting the idea that SERT may play a small role in reinforcement.   

http://www.ncbi.nlm.nih.gov/entrez/..._uids=14612142&query_hl=1&itool=pubmed_DocSum

We have to remember that we're talking about rodents here, so just because SERT inhibition isn't reinforcing by itself doesn't mean that having SERT inhibition is a bad thing when it comes to drug design (depending on your goal).  Also, theres a good chance that there's some interplay between SERT and DAT so that inhibition of SERT could add to the effects a DAT inhibitor.   

Smyth, you are right that methylphenidate has no activity at SERT, and maybe that makes it a more effective ADHD drug.  Amphetamine also has weak, although not necessarily negligible, inhibition of SERT.   Anybody have any ideas why there is this preference?  

Lastly, naphthalene *is* found in many medically relevant drugs (naproxen sodium for example).


----------



## Helios.

5-HT is not reinforcing.  DA is.


----------



## Dondante

Are you a robot?  It's not so damn simple.  

If you had read my post, you would have noticed that cocaine is reinforcing even in DAT-KO mice, but not in DAT/SERT-KO mice.  Think about it.  Or is that asking too much?


----------



## Smyth

Read some of the papers in the following link:

http://www.sciencemag.org/cgi/content/abstract/237/4819/1219

I started a thread titled "flaws in the DA hypothesis?" a few months back and we concluded that DA is indeed the chief determinant in reinforcing and psychomotor efficacy.


----------



## Dondante

Thanks for the link.  I have never doubted that DA was the primary determinant for reinforcing behavior, but what I'm saying is that other transporters might play a small role in modulating the reinforcement and psychomotor effects.  Maybe I'm flat out wrong, I don't know.  

Also, the goal here is not to create the most addictive molecule in history.  There must be a reason that specific DAT inhibitors are not on the market.  Stimulation is not synonymous with dopamine excess.   

Here's a section of the abstract I posted:



> The reinforcing potency of cocaine is maintained in the absence of the DAT but decreased in the absence of the NET; its motivational rewarding effect is observed in the absence of the SERT, but not when both DAT and SERT are lacking. Moreover, a dichotomy between cocaine motor activating and reinforcing effects is reported. Such dichotomy is suggestive of independent mechanisms underlying the psychomotor stimulant and reinforcing effects of cocaine. Overall, these studies provide evidence that cocaine dynamically acts at multiple sites through pathways that might be exchangeable under certain circumstances.





			
				Smyth said:
			
		

> The thing is, I thought the general code of conduct is that people try and discriminate against serotonin and not in favor of it.



So have we concluded that people wouldn't discriminate against serotonin?  I think it's clear that it's not reinforcing itself, but that doesn't mean that it's not a useful pharmacological attribute.  It seems to be in MDMA.  



			
				Smyth said:
			
		

> Dondante said:
> 
> 
> 
> 
> 1-Naphthalen-2-aminopropane? Any thoughts?
> 
> 
> 
> Im sure people have tried it only it wasnt very popular and has subsequently never established any sort of reputation. Still, i'd like to hear any accounts on this compound also - even negative ones, just to try and find out what the crack is wit this shit.
Click to expand...


You really think someone has tried it?  Maybe I underestimate the exploration that dedicated chemists do, but according to Shulgin, nobody ever brought it's cousin G-N (1,4-dimethoxynaphthyl-2-isopropylamine) above 2mg.  At that level there were no signs of toxicity and no central effects.  

I just realized that I missed 2C-G-N in Pihkal.  Doesn't sound too pleasant.  The one that hadn't been taken higher was G-N.  Wonder what would happen if you took off those two methoxys, and maybe added a methyl to the nitrogen.  It still might be interesting in the pyrovalerone analogue series.


----------



## Smyth

This is an interesting application of the naphthyl group. The compound shown is related to venlafaxine. It has actually been made and is not theoretical.


----------



## nuke

I hope it's more fun than venlafaxine.  That stuff kind of murdered my brain.


----------



## Dr. Beat

nuke said:
			
		

> I hope it's more fun than venlafaxine.  That stuff kind of murdered my brain.



same- ever since taking that stuff i have chronic yawning - funny the first few 100 times, but 100000 yawns later i am totally over them.


----------



## Riemann Zeta

I would be interested to see the effects of alpha-methyl-napthylethylamine (amnetamine?).  It is supposed to have dopaminergic and (unfortunately or fortunately, depending on your personal bias) serotonergic properties.  I remember reading a paper where it was used as a prototype compound for putative cocaine-dependence therapy.  It might be a kinder, gentler analogue of amphetamine.  Another interesting compound would be the N-ethyl analogue of pyrovalerone--as the stimulant character of a phenethylamine compound seems to vanish if the N-alkyl moiety is more sterically bulky than an _n_-propyl chain (or in the case of ring-closed moieties, a pyrrolidine).  And one that I have always wondered about is simply N-pyrrolidyl-amphetamine.


----------



## Helios.

N-pyrrolidyl-amphetamine is said to be somewhat active.


----------



## hussness

Riemann Zeta said:
			
		

> Another interesting compound would be the N-ethyl analogue of pyrovalerone--*as the stimulant character of a phenethylamine compound seems to vanish* if the N-alkyl moiety is more sterically bulky than an _n_-propyl chain (*or in the case of ring-closed moieties, a pyrrolidine*).  And one that I have always wondered about is simply N-pyrrolidyl-amphetamine.



Am I reading this wrong?  I thought there was a big thread here on MDPV as a stimulant.


----------



## Riemann Zeta

Both pyrovalerone and MDPV have ring-closed _N_-pyrrolidyl moieties.  This appears to be the largest ring-closed alkyl group that still confers CNS stimulant action (although, these compounds are DA reuptake inhibitors, rather than DAT substrates).  The largest (sterically) open-chain _N_-linked alkyl group that preserves CNS stimulant activity appears to be _n_-propyl, as even _N_-isopropyl amphetamines are inactive.

Interestingly, the beta-keto amphetamines (cathinones, pyrovalerones) seem to exhibit more DA reuptake inhibition activity and less DAT substrate activity than the standard beta-methylene amphetamines.  Take ethylcathinone versus _N_-ethylamphetamine or methylone versus MDMA--each cathinone congener appears to function more as a monoamine reuptake inhibitor, rather than a DAT/NET/SERT substrate.


----------



## Refluxer

fastandbulbous said:
			
		

> Fencamfamine also lends itself to a lot of fiddling and tweaking of the basic skeleton
> 
> 
> 
> 
> 
> 
> 
> Pipradrol derivatives are the one where most hope lies.
> 
> 
> 
> 
> 
> 
> Shulgin wrote about 2-(diphenylmethyl)piperidine as being a possible future drug of abuse, as it is estimated to have the same CNS stimulant properties as methamphetamine, but to be active at 2.5mg as opposed to 5mg for methamphetamine, and also to have less peripheral activity as well.
> 
> One last bit for the cocaine lovers among you.



Does anyone have first, second, third hand experience with these drugs? Pipradrol derivates included. Which ones do you think offers good alternatives to amphetamine when it comes to mental stimulation and euphoria?

Anyone actually tried the famous and easily synthed fluoro coke analog?

Replacing the ethyl group on fencamfamine with a methyl would probably make a very similar drug. Does anyone know if it has been done?

I'd also love to hear from someone that has tried amfonelic acid, can't seem to find anything else than in vitro data about it.

If a clandestine chemist would go about synthesising a drug that can match up to good ol' speed or cocaine in qualitative mental effects and would be legal in his/hers non-US jurisdiction, what different compunds do you think would come up as alternatives?


----------



## Helios.

"Potency = 60x Cocaine" => 3,4-dichlorophenyl moiety or 
3,4-methylenedioxyphenyl moiety.  Provided only, of course, that you are willing, able, inclined, and allowed to do so.


----------



## Helios.

2-benzyl-pyrrolidine.
2-piperonyl-pyrrolidine.

#9:  1-(3,4-dichlorophenyl)-1-(2-pyrrolidyl)methane.


----------



## Helios.

b-CO2Me-methamphetamine.
b-CO2Me-ethamphetamine.


----------



## Helios.

b-(CO2CH2CH3)amphetamine.
b-(CO2CH2CH3)methamphetamine.


----------



## nativenick

so do you think it would be possible to toy around with caffiene and make future analogues with more recreational potential


----------



## mad_scientist

nativenick said:
			
		

> so do you think it would be possible to toy around with caffiene and make future analogues with more recreational potential



Probably not, there have already been much stronger analogues of caffiene made, but they are not drugs of abuse. Caffiene just isn't that recreational, high doses cause anxiety rather than euphoria and with lots of nasty peripheral side effects. 

It might well be possible to make a derivative of caffiene that was more fun to take, but this would involve significantly altering the activity profile. Simply producing a more potent analogue would confer little advantage.


----------



## Smyth

Dondante said:
			
		

> Thanks for the link.  I have never doubted that DA was the primary determinant for reinforcing behavior, but what I'm saying is that other transporters might play a small role in modulating the reinforcement and psychomotor effects.  Maybe I'm flat out wrong, I don't know.
> 
> Also, the goal here is not to create the most addictive molecule in history.  There must be a reason that specific DAT inhibitors are not on the market.  Stimulation is not synonymous with dopamine excess.
> 
> Here's a section of the abstract I posted:
> 
> 
> 
> 
> 
> So have we concluded that people wouldn't discriminate against serotonin?  I think it's clear that it's not reinforcing itself, but that doesn't mean that it's not a useful pharmacological attribute.  It seems to be in MDMA.
> 
> 
> 
> You really think someone has tried it?  Maybe I underestimate the exploration that dedicated chemists do, but according to Shulgin, nobody ever brought it's cousin G-N (1,4-dimethoxynaphthyl-2-isopropylamine) above 2mg.  At that level there were no signs of toxicity and no central effects.
> 
> I just realized that I missed 2C-G-N in Pihkal.  Doesn't sound too pleasant.  The one that hadn't been taken higher was G-N.  Wonder what would happen if you took off those two methoxys, and maybe added a methyl to the nitrogen.  It still might be interesting in the pyrovalerone analogue series.



Abstract:
Monoamine transporter proteins are targets for many psychoactive compounds, including therapeutic and abused stimulant drugs. This paper reviews recent work from our laboratory investigating the interaction of stimulants with transporters in brain tissue. We illustrate how determining the precise mechanism of stimulant drug action (uptake inhibitor vs. substrate) can provide unique opportunities for medication discovery. An important lesson learned from this work is that drugs which display equipotent substrate activity at dopamine (DA) and serotonin (5-HT) transporters have minimal abuse liability and few stimulant side-effects, yet are able to suppress ongoing drug-seeking behavior. As a specific example, we describe the development of PAL-287 (α-methylnapthylethylamine), a dual DA/5-HT releasing agent that suppresses cocaine self-administration in rhesus monkeys, without the adverse effects associated with older phenylethylamine 5-HT releasers (e.g., fenfluramine) and DA releasers (e.g., amphetamine). Our findings demonstrate the feasibility of developing non-amphetamine releasing agents as potential treatments for substance abuse disorders and other psychiatric conditions.


----------



## fastandbulbous

> An important lesson learned from this work is that drugs which display equipotent substrate activity at dopamine (DA) and serotonin (5-HT) transporters have minimal abuse liability and few stimulant side-effects, yet are able to suppress ongoing drug-seeking behavior. As a specific example, we describe the development of PAL-287 (α-methylnapthylethylamine), a dual DA/5-HT releasing agent that suppresses cocaine self-administration in rhesus monkeys



That seems strange considering MDA, MDMA and methamphetamine all cause a large increase of 5HT & dopamine in their respective synaptic clefts and are noted for their abuse potential


----------



## Helios.

1-(3-chlorophenyl)-2-pyrrolidinylpropane HCl.
1-(3,4-methylenedioxyphenyl)-2-pyrrolidinylpropane HCl.


----------



## vecktor

Helios. said:
			
		

> 1-(3-chlorophenyl)-2-pyrrolidinylpropane HCl.
> 1-(3,4-methylenedioxyphenyl)-2-pyrrolidinylpropane HCl.



IUPAC tourettes strikes helios again....


----------



## Helios.

They got the idea.
You know not.


----------



## Dondante

vecktor said:
			
		

> IUPAC tourettes strikes helios again....



LOL  

... i promised myself i'd never use that lingo, but I really did laugh out loud


----------



## Helios.

^Chris Isaak strikes again.


----------



## fastandbulbous

It was actually pidgin IUPAC, the full IUPAC name for them should have included ...2-(1-pyrrolodinyl)... etc

[/pedant]


----------



## Helios.

1-phenyl-2-(1-pyrrolidinyl)propane.


----------



## vecktor

Helios. said:
			
		

> 1-phenyl-2-(1-pyrrolidinyl)propane.


close, but no cigar.


----------



## Helios.

it's not how you spell it, it's what it feels like when you take it.  that's what's important.  get it?  

should by dyl instead of dinyl?
WHO GIVES A F***


----------



## vecktor

fastandbulbous said:
			
		

> That seems strange considering MDA, MDMA and methamphetamine all cause a large increase of 5HT & dopamine in their respective synaptic clefts and are noted for their abuse potential



Quickly reading the paper indicates that there might be other effects of PAL 287 which are confusing things, the authors mention that 4-methyl ampetamine has identical activity profile and yet was a reinforcer. PAL 287 has partial agonist activity at 5HT 2c receptors, this would certainly alter the stimulant effect of massive dopamine release/ uptake inhibition. the authors hint at the problems when they suggest that PAL 287 was preventing the critters from pressing the levers even if the wanted to:


> The significant decreases in food-maintained responding suggest that decreases in cocaine self-administration may have resulted, at least in part, from nonselective effects of PAL-287



This is what Nichols tends to write off as disruption, especially when it doesn't agree with the current theory.
The earlier work of these authors correlated NE release reuptake inhiition with self administration and reinforcement.

I remember reading something about the pyretic activity of a napthylamine maybe napthylethylamine something along the lines of it being one of the most potent pyretics discovered. I don't have the book any more, if anyone has Paul Karrers Organic Chemistry from 1940 something its in there.



> "All the monkeys had histories of cocaine self-administration."


 damn those primates, stealing the stash.


----------



## Helios.

meta-chlorobenzylpiperazine, not sure if that one's been done yet or not.
meta-chloro-des-(CO2CH3)-methylphenidate.


----------



## fastandbulbous

Rather than go for 2-benzylpiperidine, the logical target should be 3-benzylmorpholine as of the the diphenylmethyl substituted heterocyclic compounds, the original paper reported the morpholine derivative to be by far the most potent locomotor stimulant in trials.

This has the extra advantage of being a few easy staps from phenylalanine (via phenylalaninol) rather than having to fuck around with expensive things like pipecolic acid & nast organometallic compounds (Grignard or organolithium)

BTW 3-benzylmorpholine has the same phenethylamine skeleton as 2-benzylpiperidine, it's just the numbering starts from a different place due to the heterocyclic oxygen atom


----------



## Helios.

namely,
3-benzylmorpholine.
3-piperonylmorpholine.
3-(meta-chlorobenzyl)morpholine.
3-(3,4-dichlorobenzyl)morpholine.
3-(3-indolyzyl)morpholine.
and so forth?


----------



## nuke

So...phenmetrazine derivatives.  Why on Earth did methylone come before 3-methyl-2-(3,4-methylenedioxy)-phenylmorpholine?  I wonder if the activity is closer to MDA.  Para-methoxy-phenmetrazine?  Hmm..  I'm guessing there's a good reason I don't know why these never happened.


----------



## Smyth

have u ever seen the patent for phenmetrazine? [The synthesis is a bitch]


----------



## vecktor

nuke said:
			
		

> So...phenmetrazine derivatives.  Why on Earth did methylone come before 3-methyl-2-(3,4-methylenedioxy)-phenylmorpholine?  I wonder if the activity is closer to MDA.  Para-methoxy-phenmetrazine?  Hmm..  I'm guessing there's a good reason I don't know why these never happened.



I suppose the reason is that methyone works in a similar way to MDMA the morpholines are much more likely to be simple stimulants. As far as I am aware there is not a lot that can be done to the side chain of MDMA without the sparkle disappearing.  N-hydroxy is OK and that is about it.
its shame that in order to get MDMA like effects the molecule has to be fairly indescriminate, adding bits on or locking up the side chain improves the selectivity serotonin versus DA but the magic is gone.


----------



## vecktor

Smyth said:
			
		

> have u ever seen the patent for phenmetrazine? [The synthesis is a bitch]



Mr Mod please delete if this is too synthesis based

surely it can be synthesised from the diketone or oximino ketone, both of which have been used in historical adrenaline synthesis. 
alternatively it should be possible to go through the B hydroxy amine.


----------



## fastandbulbous

Smyth said:
			
		

> have u ever seen the patent for phenmetrazine? [The synthesis is a bitch]



It's not - it's a condensation of norephedrine & 2-iodoethanol followed by dehydration with sulphuric acid (no I'm not going to give details as that's verboten). Equally bromopropiophenone & 2-aminoethanol gets you to the same pre-dehydration place.

I wouldn't give up on the methylenedioxy analogue of phenmetrazine as it is capable of attaining the conformation of MDEA and isn't the beta hydroxy or methoxy analogue od MDA active?


----------



## Helios.

Yes, BOB-MDA is active.  Desirable?  Perhaps not.

The MDO phen(di)metrazine analogues may be active but are most likely less desirable than the original MDxx series.


----------



## mad_scientist

fastandbulbous said:
			
		

> I wouldn't give up on the methylenedioxy analogue of phenmetrazine as it is capable of attaining the conformation of MDEA and isn't the beta hydroxy or methoxy analogue od MDA active?



beta-methoxy-3,4-MD-phenylethylamine is active (pihkal #15) so presumably the amphetamine analogue would be active also although not sure if it has been tested?

One compound i would be interested in would be the 3',4'-methylenedioxyphenyl analogue of 4-methylaminorex...the 4'-CF3-phenyl and 3',4'-dichlorophenyl analogues were highly active appetite supressants and more serotonin selective than the parent compound, so the methylenedioxy derivative might also be worth a look.

Indeed many of the amphetamine-derived stimulants are unsubstituted on the phenyl ring, so in theory methylenedioxy analogues could be made for any of them...how about the 3,4-methylenedioxy analogue of fencamfamine etc....or for that matter, even the corresponding cocaine analogue could be good, seeing as 3',4'-dichloro-cocaine is more active than the parent, and blocks both serotonin and dopamine reuptake (so less selective than coke, but with recreational drugs, "messy" binding is not always a bad thing)


----------



## fastandbulbous

If you're looking for stimulants, then yes they might be more active as dopamine reuptake inhibitors, but if you're looking for entactogenic activity it's not as simple as just sticking a methylenedioxy group on the phenyl ring (it's a lot more complicated) of a series of stimulants. The reason I mentioned the MD analogue of phenmetrazine is because it has a reasonable chance of entactogenic activity; bunging it on 4-MAR, fencamfamine isn't going to be effective simply because of the limited conformation of those ring structures


----------



## Helios.

mad scientist is thinking in the right direction.

Personally, I like stimulants, but any new entactogens are tres wilkommen.
Also, I don't know that the 3,4-dichlorophenyl thingies are either pure entactogen or pure stimulant or what.  The 3,4-dichloromethylphenidate analogue is said to be the most rewarding of that series, which would to me indicate stimulant action.  

This direction of study merits research.


----------



## Helios.

*keepin' it simple / back to basics*

'Stimulants of the Future':  3,4-dimethoxymethamphetamine HCl.

C'mon, guys, I know you can pull this one off with a little dimethylsulphate and some other standard items.  The 'geometric colored objects' [see PIHKAL] observed with 3,4-DMA in mental patients intrigues me more than just a little bit.

One time, in my dorm room, after binging on some good crank and smoking a bowl of weed, I saw a rotating, glowing green triangle in the air.  It was awe-inspiring.


----------



## hussness

fastandbulbous said:
			
		

> This has the extra advantage of being a few easy staps from phenylalanine (via phenylalaninol) rather than having to fuck around with expensive things like pipecolic acid & nast organometallic compounds (Grignard or organolithium)



I'm a little skeptical about that since I can't think of a way to reduce a carboxylic acid all the way to an alcohol without using a nasty LAH.


----------



## Helios.

^ok (maybe pressurized catalytic hydrogenation), but how hard would it be to give some anhydrous methanol, 3,4-dimethoxyphenylacetone, MeAm and NaBH4 a spin?


----------



## vecktor

*reasons why 3,4 DiMeO meth is a waste of time*



			
				hussness said:
			
		

> I'm a little skeptical about that since I can't think of a way to reduce a carboxylic acid all the way to an alcohol without using a nasty LAH.



or you could simply buy the phenylalaninol.

helios- I don't think anyone is at all interested in 3,4 dimethoxymethamphetamine. the reasoning is simple. 


if you expect it to be an entactogen like MDMA then one would expect the primary amine to show some entactogenic activity a la MDA. It doesn't, heroic doses have been eaten in the past.

then look at the modifications that can be made to the dioxole moety of MDMA adding a single carbon to the bridge carbon in MDA (to make EDA) all but abolishes activity . The dimethoxy groups of 3,4 dimethoxyamphetamine are easily as bulky as EDA's, and they are not constrained, therefore it is very very very unlikely that it will form a confguration like MDA or MDMA.

However the MethylMethoxyamphetamine is reported to substitute for MDMA to an extent. 

As a side note 3,4-dimethoxy methylamphetamine would be produced from ingestion of 4-chloro methamphetamine, not that eating 4-chloro methamphetamine is a good idea at all.


----------



## hussness

fastandbulbous said:
			
		

> Rather than go for 2-benzylpiperidine, the logical target should be 3-benzylmorpholine as of the the diphenylmethyl substituted heterocyclic compounds, the original paper reported the morpholine derivative to be by far the most potent locomotor stimulant in trials.



What is this reference?  I just did an ACS journals search and turned up with nothing.


----------



## MattPsy

Hey, you could synth that from vannillin very easy with DMS, followed by standard Amp preparation from the aldehyde.


----------



## mad_scientist

vecktor said:
			
		

> or you could simply buy the phenylalaninol.
> 
> helios- I don't think anyone is at all interested in 3,4 dimethoxymethamphetamine. the reasoning is simple.
> 
> 
> if you expect it to be an entactogen like MDMA then one would expect the primary amine to show some entactogenic activity a la MDA. It doesn't, heroic doses have been eaten in the past.
> 
> then look at the modifications that can be made to the dioxole moety of MDMA adding a single carbon to the bridge carbon in MDA (to make EDA) all but abolishes activity . The dimethoxy groups of 3,4 dimethoxyamphetamine are easily as bulky as EDA's, and they are not constrained, therefore it is very very very unlikely that it will form a confguration like MDA or MDMA.
> 
> However the MethylMethoxyamphetamine is reported to substitute for MDMA to an extent.
> 
> As a side note 3,4-dimethoxy methylamphetamine would be produced from ingestion of 4-chloro methamphetamine, not that eating 4-chloro methamphetamine is a good idea at all.




4-methoxy-3,N-dimethylamphetamine would be a good one to try, as 3-Me-4-MeO-A is supposedly similar to MDMA (in Nichol's rats anyway)

And for that matter, 2-methyl-MDA and 5-methyl-MDA were more active than MDA, with the 5- being strongest. So maybe 2,5-dimethyl-MDA might be worth a look, although that might make the ring too bulky...or perhaps 4-MeO-3,5-diMe-A...or their N-alkyl derivatives....many possibilities.


----------



## fastandbulbous

hussness said:
			
		

> What is this reference?  I just did an ACS journals search and turned up with nothing.



Will dig paper out, but I think it'd included in the rhodium archive - it's to do with pipradrol analogues & their effectiveness as CNS stimulants


----------



## fastandbulbous

mad_scientist said:
			
		

> 4-methoxy-3,N-dimethylamphetamine would be a good one to try, as 3-Me-4-MeO-A is supposedly similar to MDMA (in Nichol's rats anyway)



3-Methoxy-4-methylamphetamine is pretty much like IAP in that it is serotonogic but without much in the way of dopaminergic activity - N-methylation isn't going to suddenly make it magically like MDMA (I've tried N-methyl IAP - IMP as a friend playfully named it! - & it wasn't any sort of noticable improvement over IAP). To get the entactogenic activity, it seems that the 3-O atom nees to be constrained, not flopping around as in 3-methoxy-4-methylamphetamine (to do with lone pair orientation).

A good bet would be 6-(2-(methylamino)propyl)-2,3-dihydrobenzofuran - MDMA with the 4 oxygen replaced by a methylene group, or equally the primary amine compound (analogous to MDA). The compound with the methylene group in place of the 3-oxygen (referring to MDA not MDMA) is active but doesn't quite tick all the boxes of entactogenic activity and is best described as 'strange' (although the person calling it strange said he'd repeat it at the 200mg dosage level). Apparently the one I mention above is a bit more difficult to synthesize, but I'd recon it'd be well worth it.

Maybe at this point it's worth considering the pharmacology of mixtures of drugs. In a simplistic move, I tried combining IAP (serotonogic component) with amphetamine (dopaminergic component) and got a combined result that was more than passable as MDA in effects. This sort of simplistic approach doesn't always work, but as long as it's not contraindicated, it's definitely worth a try sometimes!


----------



## Helios.

*vektor do your homework*

Quote:  3,4-DMA, PIHKAL, p. 605:
A few non-military studies have indicated that 3,4-DMA is orally active at 160mg, and so probably its potency by this more conventional route would fall midway between that of mescaline and MDA.

What do you have to say to that?
What are you going to claim next, that TMA is not active either?


----------



## fastandbulbous

> A few non-military studies have indicated that 3,4-DMA is orally active at 160mg



Every study I've seen has stated that 3,4-dimethoxyamphetamine is inactive even at the 500mg dosage range other than some adrenergic activity (but no proper psychedelic or entactogenic activity). I'm tempted to say it looks like a typo and there should be another 0 at the end ie 1600mg or that the 160mg refers to 4-methyl-3-methoxyamphet but was misread. Without specifically citing the studies saying that, it's a bit hard to believe (remember this is just Shulgin repeating second-hand info - the original info could be corrupted or plain wrong; If there's no activity with that dose via IV, then it's not going to be more potent orally; it appears to take 600-700mg via IV to elicit psychedelic effects, so 160mg orally doesn't have a hope. Such things are always the other way around ie IV is always more potent than oral route.

Larger alkoxy groups on the 4-position produces compounds with activity under 500mg via the oral route, but not the 3,4-dimethoxy


----------



## Helios.

fastandbulbous,
^so 3,4-DM(M)A  is inactive, but 3-methoxy-4-(n)-pentylamphetamine is probably not inactive.
What is the word on 4-hydroxy-3-methoxy-(meth)amphetamine?


----------



## fastandbulbous

No, alkoxy groups - I understand that 3-methoxy-4-propionoxyamphetamine is active, (under 500mg but I cannot remember the actual dose). The 4-alkyl substituted ones are most probably active up to the 3/4 carbon chain, but I wouldn't say for definite as it's just theoretical musings about them

4-hydroxy compounds are not going to be active as there needs to be a hydrophobic group there for activity at 5HT2a and phenolic OH groups are fairly polar (and less likely to cross the BBB)


----------



## Helios.

Au contraire mon frere,
DOAM is active.
des(2-methoxy)-DOAM will be active as well, no?

Also, having one hydroxyl group does not preclude necessarily CNS penetration; see psilocin, for example.


----------



## cynosure

Church said:
			
		

> All I know is that if some of you chemists would get to making a euphoric, entactogenic amphetamine, one that doesn't necessarily cause the user to have epiphanies and psychospiritual revelations, I would pay top dollar for it.
> 
> Or, if there are still some chemists out there who aren't pussies about making drugs that are specifically controlled or illegal, would you please flood the markets with more MDA and less MDMA? Thank you.
> 
> MDA = the best recreational drug EVER!!!



I imagine that the route that these chemists are using is one in which involves tacking on one extra step for making MDA from it's ketone precursor. Other synthetic routes are longer to get MDMA, but the method most commonly used must be the former.


----------



## Helios.

Not really, either MDA or MDMA can be made in one step from MDP2P/PMK using sodium cyanoborohydride in methanol and the appropriate amine or methylamine salt. 

You can also get MDA from MDP2P/PMK using the Leuckart reaction which involves forming an amide following by hydrolysis.  This method is messier but sound.


----------



## fastandbulbous

Helios. said:
			
		

> Au contraire mon frere,
> DOAM is active.
> des(2-methoxy)-DOAM will be active as well, no?
> 
> Also, having one hydroxyl group does not preclude necessarily CNS penetration; see psilocin, for example.



From PIHKAL:



> _QUALITATIVE COMMENTS: (with 10 mg) There was a clear threshold that in no way interfered with my day's activities. I was quite gay and voluble at lunch and bubbled on into the afternoon with puns and high spirits. There may have been a little motor incoordination as noted in handwriting, and there was a strange tenseness during driving. There were no sequelae, there was no trouble sleeping, and with this potency way down from the lower homologues, I have no pressing desire to take this compound to a higher dose._




Don't sound active in any meaningful psychedelic way - in fact Shulgin's description of what happened sounds like it has more in common with alcohol than any psychedelic I can think of. Psilocin forms an internal hydrogen bond compound (forget the name of such things at the moment - my brain seems stuck on zwitterion, which it isn't) that somewhat negates the polar nature of the OH group; because of steric considerations, 4-hydroxyphenethylamines are unable to form such an internally hydrogen bonded compound


----------



## cynosure

Helios:

Not really, either MDA or MDMA can be made in one step from MDP2P/PMK using sodium cyanoborohydride in methanol and the appropriate amine or methylamine salt.


You can also get MDA from MDP2P/PMK using the Leuckart reaction which involves forming an amide following by hydrolysis. This method is messier but sound.
---

Ok ok
You're right. But that was just a trap to see who knows too much for their own good. It was already obvious that you do  
I guess what I was thinking of was the synthetic route that most small time chemists would be using with precursor acquisition being a concern. I imagine sodium borohydride and cyano borohydride are harder to come by without raising eyebrows. But if you have the ketone in hand, hydroxylamine, aluminum foil and some mercury metal are easy to come by, but add an extra step since you have to form the oxime. If you consider that a step. 
So why isn't there more MDA being produced? I imagine some of the big labs may even go through MDA as an intermediate before N-methylation to MDMA. Doesn't make good business sense. I suppose it's supply and demand. MDA freebase is even easier to distill than MDMA freebase isn't it? My knowledge is based on browsing the hive years ago, so don't use me as a reference. And it's highly unlikely that this big evil labs bother distilling the freebase anyways.

Fishing through my benzo destroyed memory, I also remember reading about the substituting PPA (or its isomers) with (pseudo)ephedrine via standard reaction conditions (whatever they were at the time, cyanogen bromide or the obviously less deadly method) . Apparently this wasn't a good drug candidate due to some adverse side effects.  Does anybody know why?

And does anyone want to suggest what the effect of replacing the oxazoline ring with an oxazole ring. Extra double bond between the two quaternary carbons. I know this change in planarity is not insignificant, the only reason I bring it up is because the different diastereomers of the parent compound all show activity. So maybe the binding site is pretty premiscous.


----------



## fastandbulbous

^ Which makes you wonder why no-one is isolating the optical isomers of MDA, keeping the more actibe R-isomer & methylating just the S-isomer to produce S-MDMA, which is the more active of MDMA's optical isomers. That way they could effectively double their output/profit as the less active isomers of both MDA & MDMA represent a waste of precursor, time, effort and money. For a bit more effort & only requiring one of the isomers of tartaric acid (if I remember correctly) to separate S-MDA from R-MDA, they could get so much more in return.

Fuck, I mean they could get optically active tartaric acid from even squeaky clean chemical firms without anybody raising an eyebrow! You'd think somebody would have noticed it considering it can effectively double profit/output (or are they doing too much of their own product, leaving them a bit befuddled when it comes to improving the business end? )


----------



## phase_dancer

^ Absolutely. But how would you _know_ it's not being done?


----------



## Helios.

fab,

PIHKAL also states that racemic MDMA is the most qualitatively desirable.
As for the DOAM quote, it sounds great to me, almost like cannabis.
Personally, I prefer an ecstasy or cannabis high to say, DOC or LSD, except on the rare occasion when I want 5-HT2a agonism.  CH3CH2OH gets into the CNS just fine.

One day, years ago, while delving deeply into the science library, I read a book that taught me the following.  THC has a benzene ring with a 
p-(n)-pentyl-2,6-dioxo(somethings)-C unit-C unit-sp2 hybridized atom.

This corresponds to psi-DOAM, with the (roughly) sp2 hybridized atom being -NH2.
And what do you know, Shulgin's description of DOAM sounds remarkably similar.

For example, smoking weed makes me "gay and voluble," it "in no way interferes with my day's activities," I eat "lunch" while stoned, and wierdly there is "a strange tenseness while driving."  

I honestly believe that no RC company or whoever will be disappointed if they synth DOAM or 2CAM.  As for 10mg being "not potent enough," I don't get it.  That is 10x the potency of e and 30x the potency of mescaline.


----------



## fastandbulbous

You can't just make those sort of intuitive leaps considering there are several compounds from cannabis that contain a 3,5-dihydroxypentyl nucleus, yet have no CNS effects (and DOAM refers to the 2,5-oxygen atom distribution). The CNS effects of THC can be abolished by fully saturating the ring containing the double bond or making that ring fully aromatic. According to your theory it should still be active as it contains the 3,5 oxygen substitution pattern in the aromatic ring containging the pentyl group. In fact THC has one of the oxygens incorporated into a pyran ring and psychedelic CNS activity is removed if the pyran ring is opened .




> Absolutely. But how would you know it's not being done?



Seizures of drugs would come back as being optically active, but no reports say they are


----------



## Coolio

I prefer S-MDMA to racemic MDMA. I'm not sure R-MDA is as qualitatively superior to racemic MDA though, even if it's more "potent" by weight. (What's potent mean anyway... 5-HT agonist activity? 5-HT release? Dopamine release?)


----------



## cynosure

I've read a forum that was just people flaming at each other about which was better, d-meth, or the racemate. To each his or her own I suppose. One thing that  I've noticed is that the combination chemicals such as MDA and MDMA are certainly more than the sum of their parts. 60 mg of either does nothing for me. 60 mg of each is better than 120 of one or the other. I still have to try 30 mg of MDE, MDA, MDMA and bk-MDMA in combination.


----------



## Helios.

^How 'bout this combo?  

10mg DOAM
10mg DOHX (...4-(n)-hexyl)
10mg DOHP (...4-(n)-heptyl)


----------



## Dr.Heckyll

fastandbulbous said:
			
		

> The CNS effects of THC can be abolished by fully saturating the ring containing the double bond or making that ring fully aromatic.



HU-210 is a very potent derivative of THC, and both its hexahydro (fully saturated) and aromatic derivatives are more potent than HU-210 ifself.


----------



## vecktor

Dr.Heckyll said:
			
		

> HU-210 is a very potent derivative of THC, and both its hexahydro (fully saturated) and aromatic derivatives are more potent than HU-210 ifself.



strictly what F&B says is true but only for THC and plain 1,1,dimethylheptyl derivatives of THC. oxidising THC to the aromatic Cannabinol CBN  produces an essentially inactive compound as does reducing it to the fully saturated compound.


----------



## fastandbulbous

As helios was referring to DOAM and it's pentyl side chain similarity to THC, that's all I was concerning myself about (compounds with the 5 carbon side chain)



> ^How 'bout this combo?
> 
> 10mg DOAM
> 10mg DOHX (...4-(n)-hexyl)
> 10mg DOHP (...4-(n)-heptyl)



What about it? Once you get to 5-cabon chains and above pasra substituted to the amine side chain, it just starts getting too big for the hydrophobic 'pocket' of the 5HT2a receptor. Although I've never actually seen any wide ranging receptor affinity studies for DOAMompounds, I'm really pretty convinced that they're not going to have any significant interaction with either CB1 or CB2 purely because they are lacking so much more of the criteria for affinity to said receptors. If it was just down to a pentyl chain and two meta OH groups then olivetil (5-pentylrescorinol - a starting material for THC synthesis) would demonstrate activity at CB1/2 (and it doesn't)


----------



## Survival0200

How many years of organic chemistry do you have to read to be able to follow up and understand all the things in this topic?


----------



## Helios.

fastandbulbous,
(remeber me from way back?)
That's not true.  The 6 and 7 carbon chain analogues of THC are even more potent than THC itself is.  DOHX and DOHP, though unsynthesized, will be likewise.  That's my hypothesis here, anyway.

from PIHKAL:  for psychedelics, keep the chain length short.  for feel good compounds, use long tail lengths.


----------



## vecktor

Helios. said:
			
		

> fastandbulbous,
> (remeber me from way back?)
> That's not true.  The 6 and 7 carbon chain analogues of THC are even more potent than THC itself is.  DOHX and DOHP, though unsynthesized, will be likewise.  That's my hypothesis here, anyway.
> 
> from PIHKAL:  for psychedelics, keep the chain length short.  for feel good compounds, use long tail lengths.



I haven't looked at SAR of cannabinoids for a long time simply because they don't really interest me. but if I remember right, one of the requirements for a THC pyran type cannabinoid is that the long alkyl chain can bend into a hairpin type shape, this is why the 1,1 dimethyl heptyl analogues are more potent as they are more likely to bend into the desired hairpin shape. the dimethyl heptyls are a five carbon chain with the alpha alpha dimethyl. Ithought  the plain straight chain heptyl is of reduced potency relative to THC, not my field so could easily be wrong though.

Also Most non-anandamide type ligands are have also two or more carbocyclic or heterocyclic rings carrying a H bond acceptor, para to the long alkyl. I guess that these interact with the same region on the receptor as the carboxylic group of anandamide, the natural ligand. DOHX has an isopropylamino para to the long alkyl dont think that will work.
As with everything, make it and taste it is the ony true way to know about 'DOHX' . its illegal here so couldn't be researched anyway.

I have never read of anandamide derivatives being used recreationally despite the fact that some of them are resistant to enzymatic degredation and work in rats.

when it comes to cannabinoids the only one that even slightly interests me is the water soluble morpholinobutyryloxy derivative of CP 55940, which should be similar potency to THC but orally active and with good bioavailibility by this route.

this seems to have veered way off topic sorry.


----------



## fastandbulbous

> from PIHKAL: for psychedelics, keep the chain length short. for feel good compounds, use long tail lengths.



Where does it say that in PIHKAL? I'm thinking it applies to the 4-alkylthio-3,5-dimethoxyphenethylamines, not 4-alkyl-2,5-dimethoxyPEA's/amphetamines. Nothing about DOAM gives even the slightest indication that it would interact with a cannabinoid receptor. I've stated all the reasons above, but if you don't believe me, then there's nothing else I can do to convince you otherwise other than to say get some DOAM & find out for yourself


----------



## Helios.

^ok, send me some.   
j/k


----------



## cynosure

*stinky stim of the future*

I haven't seen anyone using sulfur as an isoster in compounds related to cathinone. No doubt producing some stinky, low potency, possible stimulants. Single reaction should be able to replace the oxygen with the sulfur.


----------



## Helios.

sulfure smells like rotten eggs.

ain't no need to question the authority


----------



## johanneschimpo

Survival0200 said:
			
		

> How many years of organic chemistry do you have to read to be able to follow up and understand all the things in this topic?



2 semesters of O-chem and 1 of cell biology for me, plus abundant time studying on my own.
I don't follow every bit, but I get enough out of it to know everything they are talking about, to some extent


----------



## nuke

^^  Survival
I've never been to an o-chem or bio class in my life..  Most of this thread isn't o-chem anyway, it's psychopharmacology, structural/receptor geometry, neurobiology, and SARs.


----------



## everhopeful

Finding this thread will either be the most rewarding or frustrating experience I have had in years, only time will tell. I have spent a major portion of my life (yes I know I should get out more) trying to find a quality "legal" speed. I have tried a lot of the chems mentioned here, including some of the rarer ones like 2diphenymethylpiperadine, and some even rarer like 4-phenylpiracetam (should have soon). My knowledge is all empirical/practical, I have no chemistry to speak of. I would be happy to share my experiences, sourcing etc with you to have your input and ideas.

From a users point of view (this one anyway) some pns activity is good, it's how some among us measure onset. A "clean" cns only stimulant like 2-dpmp can be a little like masturbating with a local anaesthetic, lots of action, going forever, but not "feeling" a lot! I'm not saying making your own toothpaste from the inside (the dreaded tooth grit) or wearing a hole in the carpet from an uncontrollable leg tremors is a good thing, just a happy medium would be nice.

Is it ok to leave a message for someone who has left some juicy info?


----------



## Dr.Heckyll

Worry not! The day will come when it's the future, and new stimulants are there!


----------



## sciencedj

Survival0200 said:
			
		

> How many years of organic chemistry do you have to read to be able to follow up and understand all the things in this topic?



2 Years - Organic chem I and II


----------



## specialrelativity

Stimulants aren't everything. 

trip more...learn more.


----------



## fastandbulbous

specialrelativity said:
			
		

> Stimulants aren't everything.
> 
> trip more...learn more.



Brilliant, did you read the title of the thread? Because we're discussing stimulants doesn't mean we don't consider anything else in real life.

Through psychedelic use, does one learn appropriateness in commenting?


----------



## Refluxer

^  

I was wondering, what do you think about the future of ADD drugs? Will all companies go the Strattera-way just to satisfy the drughaters? Or will a company actually get a new stimulant out there that's better (in one or more ways) than the current ones? Will any companies dust off some old compounds with less side effects than ritalin/speed? Or will they just keep cashing in on the workhorses?

Tweak more...get more done.


----------



## Dr.Heckyll

That's a good question. There are plenty of compounds in the literature with improved properties compared to methylphenidate.  But I guess it's really hard to bring any stimulant compound with the slightest abuse potential to the market. Methylphenidate is a really crappy drug (short half-life etc) but is still the principal compound for the treatmanet of ADHD.

I think the underground market is more likely to come up with something new/old recycled.


----------



## nanobrain

^how's about a mothball your way with a naphthyl pyrrollidin deriv aka 1-naphthalen-2-yl-pyrrollidin-1-yl-pentan-1-one?

seems fairly epic as in nanomolar DAT / SERT / NET efficacy? although the SERT activity may make it less suited for the, ahem, ADD. now what were we talking about? ooh, look, a possum!


----------



## Smyth

^Have u even tried stuff like MDPV? It's a pure reuptake inhibitor and thus feels very different from amphetamines, which are releasers. I havent heard of any DA agonists being abused. The tetralin scaffold provides a wealth of such compounds. Compounds like apomorphine induce vomiting but I think the D1/D2 ratio may be a factor.


----------



## nanobrain

^no comment, but subjectively some say the pyrovalerones blow doors off amps. the MDPV has almost nil SERT effects...


----------



## fastandbulbous

nanobrain said:
			
		

> ^how's about a mothball your way with a naphthyl pyrrollidin deriv aka 1-naphthalen-2-yl-pyrrollidin-1-yl-pentan-1-one?
> 
> seems fairly epic as in nanomolar DAT / SERT / NET efficacy? although the SERT activity may make it less suited for the, ahem, ADD. now what were we talking about? ooh, look, a possum!




Yeah, low SERT activity will also increase the abuse potential compared with ones working purely on catecholamine transmitter systems. Not good for an ADHD medication




> no comment, but subjectively some say the pyrovalerones blow doors off amps. the MDPV has almost nil SERT effects...



In a paper about the pyrovalerones I read, the 3,4-dichloro compounds seem to be the substiutution pattern for maximum activity. Don't know if that'll confer neurotoxicity though and something a few times the potency of MDPV is frightening to think about - I've just been told of a xxxxxx (insert own insult/expletive) who dumped half a gram of MDPV into a glass of beer and drank it all! Then complained of not sleeping for days - god save us from such things...


----------



## everhopeful

*Any more on these?*

The last two are very simple compounds that are esters of pseudotropine. The benzoate ester is also known as tropacocaine and has a potency of about 0.1x that of cocaine. replacing benzoic acid with 4-fluorobenzoic acid gives a compound of aprox 0.4x the potency of cocaine; considering how easy it is to synth (and not from monitored reagents - you can actually start from atropine and get to 3-pseudotropyl 4-fluorobenzoate in a few easy steps), I'm really surprised that it hasn't shown up in street cocaine. Maybe the market is so saturated that no one thinks it's economically viable[/QUOTE]

Are you saying these would/should have the same cns and pns package as cocaine?

Has anyone heard/seen anything further on these?


----------



## everhopeful

C6H6 said:
			
		

> I'm surprised nobody mentioned amfonelic acid yet. It's a well documented, potent stimulant. One publication even concludes that it's more addictive than morphine.



Anybody tried this one? It's available on line, if you don't mind the "hand over your car keys" price tag.


----------



## nuke

^^Reread the thread, someone mentions an assay.  Until they work on the potency issue or pharmaceutically mass produce it, I don't think it'll be available to laymen like me.


----------



## everhopeful

fastandbulbous said:
			
		

> Rather than go for 2-benzylpiperidine, the logical target should be 3-benzylmorpholine as of the the diphenylmethyl substituted heterocyclic compounds, the original paper reported the morpholine derivative to be by far the most potent locomotor stimulant in trials.
> 
> This has the extra advantage of being a few easy staps from phenylalanine (via phenylalaninol) rather than having to fuck around with expensive things like pipecolic acid & nast organometallic compounds (Grignard or organolithium)
> 
> BTW 3-benzylmorpholine has the same phenethylamine skeleton as 2-benzylpiperidine, it's just the numbering starts from a different place due to the heterocyclic oxygen atom



Could you point me to these trials please?


----------



## everhopeful

nuke said:
			
		

> ^^Reread the thread, someone mentions an assay.  Until they work on the potency issue or pharmaceutically mass produce it, I don't think it'll be available to laymen like me.



Here's a link if your inclined  

http://www.pennbio.com/dopamine.htm


----------



## everhopeful

Refluxer said:
			
		

> Does anyone have first, second, third hand experience with these drugs? Pipradrol derivates included. Which ones do you think offers good alternatives to amphetamine when it comes to mental stimulation and euphoria?
> 
> Anyone actually tried the famous and easily synthed fluoro coke analog?
> 
> Replacing the ethyl group on fencamfamine with a methyl would probably make a very similar drug. Does anyone know if it has been done?
> 
> I'd also love to hear from someone that has tried amfonelic acid, can't seem to find anything else than in vitro data about it.
> 
> If a clandestine chemist would go about synthesising a drug that can match up to good ol' speed or cocaine in qualitative mental effects and would be legal in his/hers non-US jurisdiction, what different compunds do you think would come up as alternatives?



I'm on 2-(diphenylmethyl)piperidine now. Very clean. It's a "creeper" so it can be dangerous as you wait half an our and don't feel a lot, so go again. It starts off very slow and builds up over 3-4 hours. If you take it 10.00 a.m. you'll be ale to sleep that night. Much later and you might have trouble.

First time I took it my enthusiasm overtook my reason and over two hours I took (snorted) 45-50 mg. No feelings of "oh shit" but I didn't sleep for two days.

The 2.5 mg is a bit optimistic, 5-10 is more like it, depending on how you take it of course. For IV (don't myself but have been assured) or snort that dosage is OK, for ingestion 15-25  mg is more like it.

Clarity of thought, no dithering like on amps. You can eat, it is a bit of a chore but again easier than on amps. Not much "spare" locomotor activity. Pulse stronger but not much increased rate.


----------



## Smyth

Wow, I thought people were only taking the tertiary hydroxy derivative of the aforementioned compound. 

This stuff is basically like ritalin XR?

I've seen phenyl swap for esters in a number of compounds; eg. phenyltropanes, meperidine, even carfentanil (although 4-phenyl-F is still shortacting despite being crazy potent; likely a consequence of the vast steric bulk around the 4 position). 

Even though this is not new, if a blast-from-the-past resurfaces, I still think it is still relevant to this discussion. Like when Shulgin popularised MDMA which was first made 1/2 century earlier, it paved the way for future generations and helped to depolarise the black/white policies regarding drugs in general.


----------



## everhopeful

Smyth said:
			
		

> Wow, I thought people were only taking the tertiary hydroxy derivative of the aforementioned compound.
> 
> This stuff is basically like ritalin XR?
> 
> I've seen phenyl swap for esters in a number of compounds; eg. phenyltropanes, meperidine, even carfentanil (although 4-phenyl-F is still shortacting despite being crazy potent; likely a consequence of the vast steric bulk around the 4 position).
> 
> Even though this is not new, if a blast-from-the-past resurfaces, I still think it is still relevant to this discussion. Like when Shulgin popularised MDMA which was first made 1/2 century earlier, it paved the way for future generations and helped to depolarise the black/white policies regarding drugs in general.



Whoa up there Tonto, I'm not as fast as you, no chemistry. The only mention of this "ancient" stim on this site was from those who had heard but not tried, so I was trying to "fill in the gaps" for a few.
Going back to the no chemistry, could you spell out some of those "short acting.....crazy potent" stims for a dummy please?


----------



## Refluxer

Everhopeful: If you ask me, you are most welcome to fill in the gaps on all the unusual stims you have tried. :D

Have you, for example, tried the cocaine analog made from arecoline and Chloro- bromobenzene? I'm very interested in hearing reports on that series of coumpunds, and also the WIN-series.


----------



## fastandbulbous

^ I'll second that as I've heard no reports of 2-(diphenylmethyl)piperidine or 2-(diphenylmethyl)pyrrolidine in humans, just reats. As such, any human data is appreciated (esp if anybody has experience of the most potent of the series - 3-(diphenylmethyl)morpholine), as it would be for compounds such as 2-benzylpiperidine or 2-benzoylpiperidine (benzyl 2-piperidyl ketone - the heterocyclic equivalent - in terms of carbon sidechain length - to the valerophenones such as MDPV). Actually, when it comes down to it, any compound mentioned in this thread that has little or no human data.


----------



## everhopeful

Refluxer said:
			
		

> Everhopeful: If you ask me, you are most welcome to fill in the gaps on all the unusual stims you have tried. :D
> 
> Have you, for example, tried the cocaine analog made from arecoline and Chloro- bromobenzene? I'm very interested in hearing reports on that series of coumpunds, and also the WIN-series.





			
				fastandbulbous said:
			
		

> ^ I'll second that as I've heard no reports of 2-(diphenylmethyl)piperidine or 2-(diphenylmethyl)pyrrolidine in humans, just reats. As such, any human data is appreciated (esp if anybody has experience of the most potent of the series - 3-(diphenylmethyl)morpholine), as it would be for compounds such as 2-benzylpiperidine or 2-benzoylpiperidine (benzyl 2-piperidyl ketone - the heterocyclic equivalent - in terms of carbon sidechain length - to the valerophenones such as MDPV). Actually, when it comes down to it, any compound mentioned in this thread that has little or no human data.



Thanks for the welcome. Just so you know the motivation, a lot of my friends work in the mining or engineering industries and and were getting piss tested more and more. Couple this with the upcoming (where I live anyway) saliva testers (for thc, mdma, pcp, meth and amps) in every police car sometime next year and it became obvious we were going to become either jailbirds or monks!

We decided we would set out to find legal replacements for grass, speed and e's. The only "rule" was it had to be legal and it had to have an honest/similar hit to it's "parent". Ambitious I hear you say! Well yes you were dead right.

6 months later and we have settled on;

a mix of cpp and meopp (30 mg:70 mg) as an e clone (before I hear the critics chorus of "I could feed that pitiful amount to me Granny" there has been lots of testing using a wide spread of ages, sex, poly users, empty/full stomach, situation etc as we had to get a mix that suited "eveyone". If you want it tougher, double-dip.

I you want something "trippier" swap the meopp for 20 mg of pfpp.

While these work well as bzp and tfmpp had been sceduled in a few places (yes where I live too) we figured it would'nt be too long before these 'zines too were listed. Arguably under "analog" or in our case "substituted compounds" laws the two mentioned probably wouldn't make it.

So what we were experimenting with as a smoke became the focus for e replacement, Kanna. This is a stimulants thread so I won't go into the smoke side of things but Kanna (sceletium tortuosum) had come up trumps depending on how it's prepared and paired with so we got some pure mesembrine (Kanna's main active alkaloid) and have started to look at this a the e clone.

The only drama with stright mesembrine is that it is all head and no body, OK for some but we wanted it to have some "legs" as well. Tha's where the speed search came in handy. We are about to (this weekend) try mesembrine and 2-DPMP to see how this combo works. I will let you know if your interested?

So as you can see we're not really wayward lab-rats there is method to the madness. What I would really love from someone here is an educated guess for a stim that has a mix of cns AND pns activity? We're basic folk and need that bit of feedback via the pns.

Any and all suggestions gratefully received.


----------



## fastandbulbous

If you want peripheral effects, forget most or the diphenylpiperidines/pyrrolidines/morpholines as they are reuptake inhibitors with very little but central effects. For a bit of 'jangle', my money would be on 2-phenyl-3,6-dimethylmorpholine. It's a derivative of phenmetrazine that essentially has a similar dose & all the properties of that drug, but isn't specifically named in any drug laws as far as I'm aware.

As well as that, you could always try some of the alpha-alkyl-beta-keto substituted phenethylamines; a resonably good set of substance I've been informed by a friend are the N-substituted alpha-amino butyrophenones. These are not pure dopamine reuptake inhibitors (as a 5 carbon side chain disposes them towards), nor are they as rough as the equivalent propiophenones (3 carbon side chains eg methcathinone, diethylpropion). Best of the bunch are probably 2-(methylamino)butyrophenone and 2-(1-pyrrolidino)butyrophenone.

As this is an unusual request (people generally want less pns activity while retaining cns activity), give me a bit of time & I'll have a rummage through my old notes & see if there's something more suitable. I'd have suggested N-propylamphetamine as it's about 2/3rds the potency of amphet, a bit like a watered down (and as such safer) meth & uncontrolled, but amphetamine is one of the metabolites and would give unmistakable positives for amphetamine use


----------



## HeaT

probably already been posted, but CFT.

http://en.wikipedia.org/wiki/(-)-2-ß-Carbomethoxy-3-ß-(4-fluorophenyl)tropane_naphthalenedisulfonate


----------



## mad_scientist

CFT looks attractive as a novel stimulant due to its activity profile, ie similar to cocaine but longer lasting, and in one study i've seen the lab monkeys actually preferred it to cocaine (it didn't just substitute, they actually would take the CFT rather than the cocaine when both were available)

Never heard of human trials though, and i would imagine that with two chiral centres which both need to be the correct enantiomer in order to work properly, the synthesis would be too complicated to be viable for most clandestine chemists. 

Although mind you, its not actually that complex a synthesis if you just didn't care about what isomer you made, and i suppose a racemic mix would still contain 25% of the strong isomer anyway which would certainly be strong enough that it would sell successfully...


----------



## fastandbulbous

^ Because the optical properties are also linked in with the slightly strained bicyclic structure, it's more likely that one or two isomers will predominate because of things like steric considerations etc (reduction of tropinone does not lead to an equal mixture of tropine & pseudotropine, but depending upon reducing agent used produces predominantly one isomer or the other).



> Never heard of human trials though, and i would imagine that with two chiral centres which both need to be the correct enantiomer in order to work properly, the synthesis would be too complicated to be viable for most clandestine chemists.



I can see a theoretical route to it, without any real complications, from tropine/tropinone so I'd imagine any competant organic chemist should be able to see one or more as well (including reaction details etc. which I'm very rusty with). Quite surprised that it hasn't actually appeared  & been available considering dopaminergics seems to be the next biggest target after psychedelics for 'commercial' labs


----------



## everhopeful

Refluxer said:
			
		

> Everhopeful: If you ask me, you are most welcome to fill in the gaps on all the unusual stims you have tried. :D
> 
> Have you, for example, tried the cocaine analog made from arecoline and Chloro- bromobenzene? I'm very interested in hearing reports on that series of coumpunds, and also the WIN-series.



I'm sorry you'll have to spell it out for me with the "analog made from arecoline and Chlorobromobenzine", structure, cas etc  

Have tried what I was told was a coc sub once, and figured when you have to strain to notice what your getting, it's actually nothing! I was told it was tropocaine, which as I understand it is a local! As are all the rest present in commercial coc.http://www.erowid.org/archive/rhodium/chemistry/clandestine.drug.synthesis.html#cocaine

I had read/heard somewhere that the WIN's (or some at least) were considered great for treating those evil cocaine addicts because it saited their desire but gave no stimulation?


----------



## Smyth

I've had an idea for a novel application of tropinone. Some real life chemical researchers have stepped on this idea in recent years although they haven't pin-pointed the exact same structure as I. Infact I have even discussed a written draft of my idea with a senior lecturer over coffee, who has studies opioid chemistry his entire career, and he agreed that my idea was a realistic project proposal (getting funding is the tricky part).

But, on the topic of tropacocaine, im convinced that the IC50 values dont stack-up for it to be an economical choice of stimulant, if active at all (not including local anesthetic activity).

Cocaine DAT = 89nM
Tropacocaine DAT =5180nM


----------



## Dr.Heckyll

fastandbulbous said:
			
		

> I can see a theoretical route to it, without any real complications, from tropine/tropinone so I'd imagine any competant organic chemist should be able to see one or more as well (including reaction details etc. which I'm very rusty with). Quite surprised that it hasn't actually appeared  & been available considering dopaminergics seems to be the next biggest target after psychedelics for 'commercial' labs



You would have a hard time making it from tropine/tropinone, because the carboxy group is missing and needs to be attached first. It can be done, but then you get a stereoisomeric mess. Proper labs make it from ecgonine, which is debenzoylated cocaine. So if one had cocaine available, it would be a doable thing.

Apparently, the chemistry of cocaine => CFT is beyond the ability of underground chemists. Else it would be the perfect plan: conservatively, 1kg of cocaine gives 100g of CFT, which has the potency of 4kg cocaine. So you get 4 x more doses, and the shipping volume drops by a factor of 40 making trafficing much easier.

SWIM should explain that to some columbian drug lords.


----------



## Smyth

_p_-Chloro is quite a bit more potent than _p_-fluoro and also confers greater DAT selectivity. I'm not qualitatively saying either is better (because ive tried neither), but if one subscribes to the DAT hypothesis and the more bang for the buck philosophy, then surely RTI-31 takes pole-position from WIN-35,428? 

Also I know coke addicts judge the quality of their drug by how much it numbs their face. This can be easily remedied though (no need to spell it out). Also, a point worth mentioning is that phenyl-tropanes are reported to last maybe 4 x as long as coke [Perspective 2003].


----------



## HeaT

Now if only I could go down the street and get some of these super powerful cocaine analogs....


----------



## DarkCode

HeaT said:
			
		

> Now if only I could go down the street and get some of these super powerful cocaine analogs....



I'd be for that myself, a coke high that lasts 4 or 5x longer, shiit... I'd love that.


----------



## fastandbulbous

> SWIM should explain that to some columbian drug lords.



They've got more coke than they know what to do with, so they'd have little interest in a cocaine analogue (in fact they'd actively supress it outside s. America). If demand outstripped supply, then they might, but not with the current situation


----------



## Smyth

I saw on a utube video a guy selling 1kg freebase for $800 (inside Colombia). However, on TV just 2 days ago, a farmer in Afghanistan sells crude heroin for $50/kg (sometimes as low as $35).


----------



## everhopeful

Any particular reason there is no mention of piperazines here? As I understand it they are a bit of a chemists dream of a family as far as "dial up what you want" goes. They go from motion sickness pills to viagra commercially and there are at least half a dozen available which give effects from body/speedy through to visuals/trippy. I just wondered if anyone with sort of chemical knowledge some of you guys posses had looked at them?


----------



## mad_scientist

8) 

Re: piperazines...i used to work for a "party pills" company in NZ, we assessed 1-BZP, 3Cl-PP, 3-TFMPP, 4-MeOPP, 4-FPP, 3,4-MDBZP, 1-Bz-4-Me-P, 2-BZP...most of them do have moderate stimulant/hallucinogen effects and many of them were safe and effective enough that they made it to market, but i wouldn't exactly say any of the simple piperazine derivatives are gonna be the next big stimulant of the future...if any of them were actually really fun drugs then the NZ government wouldn't have let them stay on the market for so long! 

Also all of these piperazine derivatives give you a headache on comedown and some of them cause pretty severe nausea and vomiting in susceptible individuals, plus the ones with hallucinogenic effect feel mainly weird and creepy rather than an enjoyable trippy feeling. Thats the main reason that the NZ government has allowed them to remain legal so far, because the negative side effects are so prominant that at large or frequent doses you just mainly feel like crap, hence the abuse potential tends to be rather low...


----------



## Helios.

^Piperazines are less desirable than the common stimulants available today such as:
cocaine 
amphetamine
methamphetamine
methylphenidate
MDMA, rarely MDA
caffeine

Therefore, if they do hang in there and remain available until the future comes, it will be in spite of the fact that they are less desirable than the ones we often use today, not because of it.

Has anyone tried (d)-Bz-2-Piperidine HCl yet and known it?
I have.  It is better than my previous two favorites, MDMA and meth.

Please refrain from personal flames or any other comment regarding the validity of my recent experience (the details of which you know nothing of) both unless and until you have repeated stated experience.  I did less than a gram; stayed up for 4 to 5 days.  Marked pupil dilation throughout.  Tastes similar to ice but more minty.  Looked like high quality powdered coke.  Calmer and less jittery, paranoid and tweaky than meth but lasts just as long.  Did two medium sized lines once and things started to get freaky; I was talking out loud nonstop in rhymes off the tip of my tongue from the depths of my soul without following a mould to see where this state of being would lead I could go on I guess ad infinitum but you shoulda by now have gotten the point assuming you read even the last few lines of this joint.


----------



## everhopeful

mad_scientist said:
			
		

> 8)
> 
> Re: piperazines...i used to work for a "party pills" company in NZ, we assessed 1-BZP, 3Cl-PP, 3-TFMPP, 4-MeOPP, 4-FPP, 3,4-MDBZP, 1-Bz-4-Me-P, 2-BZP...most of them do have moderate stimulant/hallucinogen effects and many of them were safe and effective enough that they made it to market, but i wouldn't exactly say any of the simple piperazine derivatives are gonna be the next big stimulant of the future...if any of them were actually really fun drugs then the NZ government wouldn't have let them stay on the market for so long!
> 
> Also all of these piperazine derivatives give you a headache on comedown and some of them cause pretty severe nausea and vomiting in susceptible individuals, plus the ones with hallucinogenic effect feel mainly weird and creepy rather than an enjoyable trippy feeling. Thats the main reason that the NZ government has allowed them to remain legal so far, because the negative side effects are so prominant that at large or frequent doses you just mainly feel like crap, hence the abuse potential tends to be rather low...



Never got to try bzp but i heard it was a hard comedown.

cpp has the ability to cause nausea in some people even at a low 40 mg dose, while others can happily take 120 mg and feel no sickness, but it's always the same people so i guess its a sensitivity thing.

meopp is a pussycat, never had anyone complain of nausea right up to 300 mg and no comedown that i've ever heard of.

pfpp is one of those chems you take and 15 minutes later you can "taste" it, hard to define, it just "feels" dirty. no nausea but feel a bit grubby the following day.

never tried the others, variations on the theme i had been told by a long time kiwi seller.

they are a lot stronger and certainly longer lasting than a lot of the stuff around, especially when you read a couple of eu reports on confiscated pills around 20+ countries in europe. i guess buying pharms straight from the factory can spoli you.

seeing as how they have a 'zine now that is supposedly 100+ times stronger them morph with the same effect, the question was is this family capable of being tweaked to produce whatever you want?

is it just that so far "back room" engineers have'nt started playing with them?

maybe its a short history with most of the experience and commercialisation in the southern hemisphere?


----------



## everhopeful

Helios. said:
			
		

> ^Piperazines are less desirable than the common stimulants available today such as:
> cocaine
> amphetamine
> methamphetamine
> methylphenidate
> MDMA, rarely MDA
> caffeine
> 
> Therefore, if they do hang in there and remain available until the future comes, it will be in spite of the fact that they are less desirable than the ones we often use today, not because of it.
> 
> Has anyone tried (d)-Bz-2-Piperidine HCl yet and known it?
> I have.  It is better than my previous two favorites, MDMA and meth.
> 
> Please refrain from personal flames or any other comment regarding the validity of my recent experience (the details of which you know nothing of) both unless and until you have repeated stated experience.  I did less than a gram; stayed up for 4 to 5 days.  Marked pupil dilation throughout.  Tastes similar to ice but more minty.  Looked like high quality powdered coke.  Calmer and less jittery, paranoid and tweaky than meth but lasts just as long.  Did two medium sized lines once and things started to get freaky; I was talking out loud nonstop in rhymes off the tip of my tongue from the depths of my soul without following a mould to see where this state of being would lead I could go on I guess ad infinitum but you shoulda by now have gotten the point assuming you read even the last few lines of this joint.



certianly agree on most you got there, its that leagal angle that spoils a good day. ritalin has always felt a tease to me, it feels like your on the way but you never seem to make it. you must be able too get hell coffee where you are! just kidding, caffeine has always given me more cramps than amps.

really interested in your chem there, any names, places? on site os your call


----------



## everhopeful

does this look promising? http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1395211#R9


----------



## hussness

Speaking of that article, why does nocaine have the opposite stereochemistry from cocaine at the 3 position?  I thought 3beta, 4beta would have conferred the most potency.


----------



## Smyth

It was argued that the 3-alpha stereochem makes the compound less addictive. You can find alot of the discussion if you run a search on JPET. 

However an interesting document that I want to show you is shown here: %)


----------



## everhopeful

Smyth said:
			
		

> It was argued that the 3-alpha stereochem makes the compound less addictive. You can find alot of the discussion if you run a search on JPET.
> 
> However an interesting document that I want to show you is shown here: %)



thanks for the info. i remember some saying tropane synths were not for the faint hearted? as i'm not capable, i use a couple of small companies in china to turn dreams into reality and they are a gen or so behind, confidence wise if not in technique, and often won't attempt anything tricky, or reported to be so.

that's why i hoped someone well schooled could give me an honest opinion as to which coc analog(s) were the best combination of potency with a not-too-frightening synthesis


----------



## Smyth

Take your pick from the attached selection. You be the judge.


----------



## Refluxer

everhopeful said:
			
		

> that's why i hoped someone well schooled could give me an honest opinion as to which coc analog(s) were the best combination of potency with a not-too-frightening synthesis



EDIT: Oops, no synthesis discussion.  

Ok, check this one out.

http://www.erowid.org/archive/rhodium/chemistry/cocaine.analog.arecoline.html

Easy synthesis, and according to a report I read the high was worthwhile. Not much PNS-activity though.


----------



## everhopeful

Refluxer said:
			
		

> EDIT: Oops, no synthesis discussion.
> 
> Ok, check this one out.
> 
> http://www.erowid.org/archive/rhodium/chemistry/cocaine.analog.arecoline.html
> 
> Easy synthesis, and according to a report I read the high was worthwhile. Not much PNS-activity though.



cheers i'm on it. i'll let you know what turns up/out. thanks again :D


----------



## hussness

I'm going to try not to tresspass here, but one word "Mannich".



			
				everhopeful said:
			
		

> thanks for the info. i remember some saying tropane synths were not for the faint hearted? as i'm not capable, i use a couple of small companies in china to turn dreams into reality and they are a gen or so behind, confidence wise if not in technique, and often won't attempt anything tricky, or reported to be so.
> 
> that's why i hoped someone well schooled could give me an honest opinion as to which coc analog(s) were the best combination of potency with a not-too-frightening synthesis


----------



## fastandbulbous

hussness said:
			
		

> I'm going to try not to tresspass here, but one word "Mannich".



That starts with the diester ofacetonedicarboxylic acid so you end up with 2 methoxycarbonyl groups. Wonder if two groups has any significance on activity? (no reason why, just curious)


----------



## Dr.Heckyll

It's easy to split off only one of the 2 methoxycarbonyl groups thermally. So this is a very viable route.


----------



## hussness

^Is there an asymmetric process for this?


----------



## hebb22

^ 
Wow, you guys sound like scientists. I think that amphetamines have potential to become more potent and last much longer. I don't know how much longer you want them to last though, i couldn't imagine a high lasting more than 48 hours. It would also be cool to see something neat happen to weed. Like if they combined weed with some really cool plant that completley altered the effects. Im sure they already have just haven't mass produced the idea yet.


----------



## hussness

^You guessed right.  Most of us sound like scientists because we _are _scientists.


----------



## fastandbulbous

hussness said:
			
		

> ^You guessed right.  Most of us sound like scientists because we _are _scientists.



I'm not; I'm a child let loose in an adults world!


----------



## Refluxer

^ Haha, same here. I wonder how I will tackle hierarchy and the intrigues, that come in both the academic world and the commercial world, when I have graduated. I've got the impression the big corporate world attract many careerists who mind their wallets and prestige more than their fellow humans. And the academic world also seems somewhat deranged.

All I want is a playground (i.e. lab) and not too much stress. I wonder if that equation will be solvable.


----------



## Refluxer

Moderators: Delete this post if it crosses the line.



			
				everhopeful said:
			
		

> cheers i'm on it. i'll let you know what turns up/out. thanks again :D



Also, altering the reaction temperature alters the isomeric composition of the final product, so using dry ice to cool the reaction will give a different product than just using ice water. If you do some searches in article databases there are a few articles that discuss these analogs and contain activity measurments of both structural and stereo isomers.


----------



## Refluxer

2-benzylpiperidine just turned up at a notorious vendor. Actually he states the content is "N-2-benzylpiperidine" which doesn't really make sense, so I assume it is 2-benzylpiperidine.

Anybody tried it? It looks promising, and should last a while longer than methylphenidate. What about comparing it to amphetamine, what differences in activity will the alifatic parts of the piperidine-ring have?

Also, what effect does the COOMe-group in methylphenidate have in terms of activity/affinity? Does it add DARI-activity or does it just make methylphenidate less toxic/easier to eliminate/metabolize?


----------



## Smyth

Here is the latest installment on work done in the field of cocaine replacement therapy:

http://www.ncbi.nlm.nih.gov/entrez/..._uids=17105829&query_hl=4&itool=pubmed_docsum


----------



## fastandbulbous

> Also, what effect does the COOMe-group in methylphenidate have in terms of activity/affinity? Does it add DARI-activity or does it just make methylphenidate less toxic/easier to eliminate/metabolize?



Gives the body a big polar group to facilitate excretion. Not sure if that was the intention, but as benzypiperidine had chance to last for a long time compared with methylphenidate, that's why it'll be the preferred compound (or else why don't they use something like pipradrol for treating ADHD?)


----------



## vecktor

Refluxer said:
			
		

> 2-benzylpiperidine just turned up at a notorious vendor. Actually he states the content is "N-2-benzylpiperidine" which doesn't really make sense, so I assume it is 2-benzylpiperidine.
> 
> Anybody tried it? It looks promising, and should last a while longer than methylphenidate. What about comparing it to amphetamine, what differences in activity will the alifatic parts of the piperidine-ring have?
> 
> Also, what effect does the COOMe-group in methylphenidate have in terms of activity/affinity? Does it add DARI-activity or does it just make methylphenidate less toxic/easier to eliminate/metabolize?



it states "N-2-benzylpiperidine dihydrochloride" 2-benzyl piperidine with one nitrogen atom cannot form a dihydrochloride whereas benzylpiperazine BZP with two can. so who knows what this is?


----------



## nuke

^^  Yup.  The fins are saying it's tasty and long lasting (8-16 hours) with a good dose being between 50-150mg.


----------



## Smyth

I know of a way to make 4-phenyl-piperidines that uses a route where there is essentially no risk of forming tetrahydropyridine style intermediate by-products.


----------



## Helios.

Gee, I wonder who thought of that compound?


----------



## haribo1

BTCP, the PCP analog (or better still it's pyrollidine analog) are supposed to substitute for cocaine in rats and lasts 6 hours. The antidepressant Aminepitine is supposed to give a good high when you begin treatment and is associated with addiction. I wonder a lot about aminepitine, I keep thinking that amongst the research papers will be some more euphoriant analogs. Easy to make and legal.
Oh and CFT can, apparently be made stronger and longer lasting by replacing the methyl ester with an isopropyl ester. I'm looking for the link but it was somewhere reputable.


----------



## Helios.

3-MeO-methamphetamine HCl.

^^haha, see my latest journal entry (12/06/2006), suckas!


----------



## 029

the drugs of the future are the one's not used today ! .. lol
ok, i', dreaming here, but the ultimate drug(s) would be ones capable of something like an on-off switch .. i.e. you could "stop" your roll with a temporay blocker and then you'd be back where you left off ..


----------



## vecktor

haribo1 said:
			
		

> BTCP, the PCP analog (or better still it's pyrollidine analog) are supposed to substitute for cocaine in rats and lasts 6 hours. The antidepressant Aminepitine is supposed to give a good high when you begin treatment and is associated with addiction. I wonder a lot about aminepitine, I keep thinking that amongst the research papers will be some more euphoriant analogs. Easy to make and legal.
> Oh and CFT can, apparently be made stronger and longer lasting by replacing the methyl ester with an isopropyl ester. I'm looking for the link but it was somewhere reputable.



In one of the animal studies of BTCP, there was excess mortality in the BTCP treated rats over the cocaine or saline treated rats. On examination there was evidence of damage to the GI system and the liver.
(psychpharmacology 1999 145 p 370-377)
There is also evidence that unlike cocaine BTCP is not a substrate type dopamine and NE releaser. Anecdotal reports suggest that BTCP is almost without effect in humans.

CFT is just one of a huge family of phenyl tropanes, stronger is a difficult thing to quantify, it is not potency, DOB for example is 20 times more potent than 2-cb it is not 20 times stronger, it just requires 20 times less to give the same effect. If potency is the measure then replacing the methyl with ethyl or isopropoxy increases the potency, replacing the entire ester moiety with a short alkene or aryl alkene also increases potency and duration of action. replacing the ester moiety with a cyclic bioisostere such as the oxazoline group increases duration without effecting potency.
the para substituent on the phenyl can also be replaced with iodine or methyl or pretty much anything. CFT has a lot of papers on it because of the fluorine can be replaced with radiofluorine and then used as a marker in PET scanning, supposedly CFT scanning to reveal the DAT density can reveal parkinsons disease earlier.
from memory I think the parachloro and its metabolically soft isostere paramethyl are more potent than CFT. 
 It is often the case that the most potent analogue is not the most interesting but it is in the world of research ligands, SAR and receptor mapping, because the theory is that the most potent ligand is closest in shape to the binding site and therefore finding more and more potent ligands can allow the binding site to be mapped.  Whether the most potent ligand is ligands the most valuable pharmaceutical is another matter entirely, DOI versus DOC for example.


----------



## vecktor

Helios. said:
			
		

> Gee, I wonder who thought of that compound?



several bees long long before you.


----------



## everhopeful

sorry to be a pain guys but as all the brain power resides in this forum i wonder if anyone can help please?
i got some carphedon (4-phenylpiracetam or phenotropil) made and was all excited when it turned up. as the dose on the net etc at 100-150mg i thought my supercautious 5-10mg "tester" was, apart from uncharacteristic, pretty safe.
i got ringing in my ears, bad taste in my mouth, assorted muscle pains and muddled head within 10 minutes and it lasted for hours.
i had been taking stims for 8 out of the last 10 days so my dilema is i can't be sure if it's the chem or me?
i queried it with the supplier (he has made stuff for me before and no probs) and he was adamant it was all ok.
he has sent me an analysis/report but neither i nor anyone else i have shown it to seems to be able to make sense of it, can anyone help out please?
i can't put an image up here unless it's on a site (same as the link button really?) does anyone know a way of posting it or sending it?


----------



## Helios.

^don't worry.  I'm sure it was real; it's just that it's a shit drug.


----------



## nanobrain

gosh, how i hate sayin' told you so...


----------



## Helios.

N-hydroxy-methamphetamine.


----------



## haribo1

Amfonelic acid is this, right?






That doesn't look fun to make. Its SAR is very interesting. You can buy 100mg for $126, has anyone tried it yet?


----------



## Helios.

2-benzyl-pyridine.
2-piperonyl-pyridine.


----------



## haribo1

Helios. said:
			
		

> 2-benzyl-pyridine.
> 2-piperonyl-pyridine.



Where's the carboxylic acid in that name? I got the image from a site selling the stuff so either they got it wrong or you did?


----------



## Helios.

There is no carboxylic acid functional group in either of the two compounds I just thought of.


----------



## Refluxer

A photo of the tablets claimed to contain either 50 or 100 mgs of 2-benzylpiperidine surfaced:






They are huge, but the effects people claim they have show they contain a stimulant of some sort. An analysis of them would be wonderful.


----------



## hussness

^So do you know yet whether it's 2-benzylpiperidine or 2-benzylpiperazine?


----------



## Refluxer

No idea. The picture is not mine, I just found a link. If I had unrestricted access to GC/MS/NMR I'd buy some and analyze it - but I don't.


----------



## Helios.

Supposedly they are piperidine things.  But there is somewhat of a language barrier going on here.


----------



## fastandbulbous

Helios. said:
			
		

> 2-benzyl-pyridine.
> 2-piperonyl-pyridine.



Once you turn the heterocyclic ring aromatic you get a change in activity, generally to the detriment. An even better compound would be 3-benzylmorpholine which has the same phenylisopropylamine skeleton that most stimulants have, but of the pipradrol derivatives made by altering the nitrogen heterocycle ring, the morpholine derivative proved to be the most potent. This also applied to the compounds where one of the phenyl groups was replaced by a hydrogen, which includes 2-benzylpiperidine. The fact that in the case of amfonelic acid the nitrogen is in an aromatic ring makes this a weird compoiund in my eyes!


----------



## Helios.

^We've already covered the 2-morpholinyl things.


----------



## fastandbulbous

Helios. said:
			
		

> ^We've already covered the 2-morpholinyl things.



Not very well then as they're actually '3-morpholinyl things' as the ring numbering starts on the oxygen, not the nitrogen.

I was simply pointing out that the morpholino derivatives of compounds containing only one aromatic ring (eg 2-benzylpiperidine) follows the same potency sequence for the different heterocyclic rings as does the compounds with 2-aromatic groups (eg. pipradrol, 2-(alpha, alpha diphenylmethyl)piperidine etc) in that the best of both groups are the morpho;ine derivatives; everybody seems dazzled by 2-benzylpiperidine yet the morpholine derivative would be a much more simple synthesis


----------



## Helios.

A lot of if has to do with availability.  

As for simplicity / elegance of synthesis:

(1) Benzene or 1,3-benzodioxole + d-2-(CO2H)-piperidine + hypophosphorous acid
(2) H2N-NH2, KOH.

If you want it your way, I don't see why d-3-(CO2H)-morpholine couldn't be substituted for d-2-(CO2H)-piperidine in the above outline.

I'm not disagreeing with that which you say in any way, except my outline looks about as simple as it gets.


----------



## Refluxer

I just thought of sticking a second phenylring at the 1 position on amphetamine, i.e. 1,1-diphenyl-2-aminopropane. I realize this will make the molecule much more clumsy/bulky, but since several other stimulants have a similar structure maybe it can have activity? And you can also expand this to several other symmetric isomers.

Anyone heard about this one? I'm sure it has been examined somewhere sometime.


----------



## MattPsy

Something similar, (S)-diphenyl-2-pyrrolidinyl-methane, is a CNS stimulant active in dosage of 25mg to 100mg...


----------



## vecktor

Helios. said:
			
		

> A lot of if has to do with availability.
> 
> As for simplicity / elegance of synthesis:
> 
> (1) Benzene or 1,3-benzodioxole + d-2-(CO2H)-piperidine + hypophosphorous acid
> (2) H2N-NH2, KOH.
> 
> If you want it your way, I don't see why d-3-(CO2H)-morpholine couldn't be substituted for d-2-(CO2H)-piperidine in the above outline.
> 
> I'm not disagreeing with that which you say in any way, except my outline looks about as simple as it gets.



not quite, for elegance and simplicity, commercially available 2-benzyl pyridine 1 step to 2-benzyl piperidine.


----------



## Helios.

It (the 2 phenyl amphetamine) won't have any more chiral centers.

vecktor,
yes that's even easier with some hydrogenation.

However, my dear <0,0,0> to <x,y,z> for a given time being, your way results in racemic 50/50 d/l R/S 2-benzylpiperidine while my, slightly--only slightly--more complex method, being stereospecific, spits out pure d-2-benzylpiperidine.

Availability of starting precusor compounds is always an impotant considerartion either way.

"Things should be made as simple as possible to be correct, but no simpler."--Einstein.

d-benzylpiperidine is 2x as valuable as racemice 2-benzylpiperidine.


----------



## fastandbulbous

MattPsy said:
			
		

> Something similar, (S)-diphenyl-2-pyrrolidinyl-methane, is a CNS stimulant active in dosage of 25mg to 100mg...



Ah, but the heterocyclic compounds are different beasts to the amphetamines. Whereas the heterocyclic compounds are reuptake inhibitors, amphetamines cause neurotransmitter release as well as inhibiting reuptake so it's not clear cut as to what the action of 1,1-diphenyl-2-propylamine. I've thought about that several times in the past but was never able to dig up much in the way of pharmacological info. On that same basis I've also wondered about beta carbon substitution of a methyl group to give 2-phenyl-3-butylamine (alpha, beta dimethylphenethylamine); this does introduce another chiral centre though so you've then got 4 isomers possible


----------



## Smyth

The butane compounds have been looked at in the past on a paper concerning conformationally rigid meth analogs. Data extracted from the article is included in the attachment. Nothing too exciting but worth viewing for information purposes.

There's been alot of work by Rothmann on dual 5HT/DA releasers lately. A quick search on JPET will yield the relevant documentation. It seems that they are quite anorectic even though they are in no way reinforcing/rewarding. This has been attributed to activity at the 5HT2C receptor subtype. It's doubtful that these compounds represent stimulants of the future but it still represents present day research in the treatment of stimulant abuse.


----------



## Helios.

Is it just me or do DA/5HT reuptake inhibitors generally suck?


----------



## Refluxer

EDIT: I was whoozy in the head and thought I read something else.


----------



## Refluxer

I would greatly appreciate if anyone could help me find the following article on 2-DPMP:

J. Tripod, Experientia, 1954, Vol. 10, p. 261


----------



## Helios.

fastandbulbous obviously gets credit for this one:
3-benzyl-morpholine HCl.


----------



## Refluxer

Nevermind.


----------



## Refluxer

Fast and *bulby*:

You mentioned 2-phenyl-3,6-dimethylmorpholine earlier. Can you dig up any references as I'm interested to read some more. And how about that molecule but with 3,5 substitution instead?

EDIT: Satisfied now, huh? :D


----------



## Helios.

Are you looking to invent something new (stimulant, opiate, psychedelic or entactogen?), test as many already existing known compounds as possible, find the best high ever, make a ton of money or just play around at work/school/multinational pharmaceutical research company?

You are hereby, to quote Wu Tang, cordially invited "take a free ride on my thoughts."  PM me if you want.  Tell me what kind of 100% legal chemical information you are seeking.  I have been around the block a time or two, and I LIKE teaching people stuff they don't know but want to learn.


----------



## fastandbulbous

Refluxer said:
			
		

> Fast and fab:
> 
> You mentioned 2-phenyl-3,6-dimethylmorpholine earlier. Can you dig up any references as I'm interested to read some more. And how about that molecule but with 3,5 substitution instead?




Who, WHO? I know I'm wonderful but I don't feel the urge to communicate said gorgeousness in my name (quite a few people seem to think my name is fastandfabulous)!  . Could be worse - one rather upset BL on the receiving end of some moderation thought to amuzingly call me fastandfuckedinthearse... What can you do in the face of the wit of a modern day Oscar Wilde!

2-phenyl-3,6-dimethylmorpholine wqs one of the battery of compounds fed to rats during my short bout of academia (I'll try and find my notes, but it's from 20-odd years ago & the spare room is full of crap that needs to be sorted); the reason it stuck in my mind, other than not being a controlled substance, is that the phenmetrazine series are quite a simple synth from phenylpropanolamine (no synth details for obvious reasons). The 3,5 dimethyl compound behaves more like an N-isopropyl substituted sympathetic agent (more peripheral effects such as pounding heart, dry mouth, sweating etc) and is possibly stearically hindered about the amine function due to increased rigidity conferred by the morpholine ring (expressed as only having a fraction of the locomotor stimulant/appetite supressant activity of the 3,6 or parent phenmetrazine)


----------



## Refluxer

Allright, thanks for the info. So you don't know if there is any published data on it except in your thesis? (Which, BTW, would be an interesting read. PM me if there is a possibility of reading it. PDF?)

I think I will have to go search some patents or something.


Helios: Why don't you educate us all instead?


----------



## Dr.Heckyll

fastandbulbous said:
			
		

> 2-phenyl-3,6-dimethylmorpholine


There's acutally a patent on this compound:





> Bibliographic Information
> 
> 2-Phenyl-3,6-dimethylmorpholine.     Siemer, Harm; Doppstadt, Adolf.  (Ravensberg G.m.b.H. Chemische Fabrik).    (1963),     2 pp.  DE  1143201  19630207  Patent  language unavailable.    Application: DE  19570710.  Priority: DE  19570710.  CAN 59:15657    AN 1963:415657    CAPLUS
> 
> Patent Family Information
> 
> Patent No.	Kind	Date	Application No.		Date
> DE	1143201		19630207	DE	1957-R21461	19570710
> 
> Priority Application
> DE			19570710
> 
> 
> Abstract
> 
> The title compd. (I) is an appetite depressant and exerts mild central stimulation.  A suspension of 165 g. 2,5-dimethyl-2,5-dimethoxy-3,6-diphenyl-1,4-dioxane, 115 ml. H2O and 80 ml. concd. HCl was refluxed, cooled, and neutralized.  The yellow oil was sepd., dissolved in 100 ml. MeOH, 75 g. H2NCH2CH(OH)Me added and the whole refluxed 0.5 hr.  Then Raney Ni (25 ml.) was added, the mixt. heated to 110° with H of 150 atm., the catalyst removed, the alk. filtrate neutralized with HCl in MeOH, and the solvent distd.  The residue was heated with 134.3 g. ZnCl2 to 220°, the melt dissolved in H2O and made alk. by aq. Na2CO3.  The oil was taken up in ether and fractionated to give I (64%), b1.5 118-20°, m. 64-5° (ether-petr. ether); HCl-salt m. 169-70°.


----------



## Refluxer

Thank you very much Heckyll!

Where can one find a good search engine for patents?


----------



## Dr.Heckyll

www.cas.org


----------



## Refluxer

Haha, embarassing. :D


----------



## ebola?

>>Fast and fab>>

Heh...so people here don't listen to Beefheart...

ebola


----------



## Helios.

The best, most long lasting, most outstanding, conscioiusness expanding, 
mind-manifesting stimulant is greater than 70% pure, recrystallized from a minimum amount of boiling water methamphetamine hydrochloride (2-methylamino-1-phenyl-propane hydrochloride crystals).

I if you are worried about undenialalbe bodily and or mental toxicity, swtich to 
(d)-2-benzylpiperidine.

Have I made my two points clear? [no caps lock used]
Phendimetrazines, as Butthead will tell you, SUCK.


----------



## fastandbulbous

> Phendimetrazines, as Butthead will tell you, SUCK.



^ Phendimetrazine isn't up to much as it's a tertiary amine and they're not much cop in heterocyclic anorexiants/locomotor stimulants. Once you move the methyl group around the ring you're back with a secondary amine, which is what you want. All you have to do is make sure the extra methyl group doesn't 'get in the way' of binding. Phenmetrazine (the parent secondary amine) is far, far from sucky. The reason Scandinavian governments went apeshit about stimulant use is because of IV phenmetrazine abuse (which is said to be more euphoric than the amphetamines)




> Which, BTW, would be an interesting read. PM me if there is a possibility of reading it. PDF?



I'd love to think I'd been let loose on a Ph.D., but it wasn't a full blown thesis (I'm far too lazy for that!) - it was part of a research project by one of the lecturers I had while doing my degree and only had the clout to produce an M.Sc., so I was reduced to an _et. al._ on the paper.




> Heh...so people here don't listen to Beefheart...



I know - uncultured heathens, the lot of 'em!


----------



## Refluxer

fastandbulbous said:
			
		

> The reason Scandinavian governments went apeshit about stimulant use is because of IV phenmetrazine abuse (which is said to be more euphoric than the amphetamines)



I've read about it to, that the speed freaks actually preferred Preludin/Fenmetrazin/Fenmetralin. That's why I got interested in your find. :D I thought they had banned all the possible close analogs to the famous phenmetrazine, especially one so similar like the one you mentioned.

Maybe I should go try find someone old enough to have experienced the era first hand and see if the claim is true...


----------



## Refluxer

Helios. said:
			
		

> I if you are worried about undenialalbe bodily and or mental toxicity, swtich to
> (d)-2-benzylpiperidine.



Even though I'm unsure of the contents of the tabs sold that claim to contain 2-benzylpiperidine, the effects people describe show it's clearly a decent stimulant of some kind. But it doesn't really sound like the stimulant-dream-come-true. Pretty tough side effects and harsh comedown. Maybe people are just overdosing, I don't know. If someone has ready access to analysis instruments, maybe I can get ahold of a pill or two and send you. It would be very interesting to see analysis of these ones.


----------



## Helios.

I've done was it either phendimetrazine or phemetrazine and it was smooth but it just didn't give me that thought rush of energy that ice does.  The Scandinavian druggies were probably IVing it based on easy of availability more than anything.

These people got the name right except for the N part.  I'm sure that's what it is.  Its degree of optical rotation--which can easily be determined with either an analog or digital polarimeter--will indicate which method of synthesis has been used.

And kittyinthedark describes 2-piperonylpiperidine as "tasty."


----------



## Canis aureus

Has this: http://en.wikipedia.org/wiki/(-)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane_naphthalenedisulfonate 

been discussed here? 


I would be intereested in cocaine analogs, more potent and longer lasting.


----------



## Helios.

Cocaine itself is already so valuable it makes its use as a precursor prohibitively expensive for almost all uses.  

Synthetic routes to new, improved cocaine analogues not involving cocaine as a starting material tend to be either similarly horrendously expensive and or complex.


----------



## fastandbulbous

Due to the efficiency of dopamine reuptake inhibitors like MDPV & pyrovalerone, I think a much better (and easier to synth) proposition is 2-benzoylpiperidine


----------



## Dr.Heckyll

Now you need to reduce the ketone to the alcohol, prepare the acetate, separate the isomers, and you get the well known stimulant levophacetoperane, which is sort of the reverse ester of methylphenidate.


----------



## haribo1

I know this sounds dumb, but I REALLY enjoyed 4MAR but plain MAR is supposed to be about 4 times more potent. The strongest of the series (ED50) was the 4-fluoro. Now, I know 4-F amphetamine isn't quite as speedy but a bit more happy. Wouldn't pFMAR be worth giving the once over? That or possibly a pseudohalogen?


----------



## Survival0200

Dr.Heckyll said:
			
		

> well known stimulant levophacetoperane


_Well known_? :D Has it been commercialized anywhere or so?


----------



## Morninggloryseed

haribo1 said:
			
		

> I know this sounds dumb, but I REALLY enjoyed 4MAR but plain MAR is supposed to be about 4 times more potent. The strongest of the series (ED50) was the 4-fluoro. Now, I know 4-F amphetamine isn't quite as speedy but a bit more happy. Wouldn't pFMAR be worth giving the once over? That or possibly a pseudohalogen?



4-MAR is 4-Methyl-Aminorex.  What do you mean "plain MAR"?  Do you mean Aminorex without the para-methyl?

With that in mind, there can be no such thing as "pFMAR" as aminorex can either have an para-alkyl or a para-fluoro...but it can't have both.  I assume you mean 4-fluoro-aminorex.


----------



## Dr.Heckyll

Survival0200 said:
			
		

> _Well known_? :D Has it been commercialized anywhere or so?


Yes, in France as lidepran (http://www.psychotropics.dk/usr_vie...lphabetical+index&historyline=&Catalogtype=A), and it's a UN scheduled substance.


----------



## haribo1

morninggloryseed said:
			
		

> 4-MAR is 4-Methyl-Aminorex.  What do you mean "plain MAR"?  Do you mean Aminorex without the para-methyl?
> 
> With that in mind, there can be no such thing as "pFMAR" as aminorex can either have an para-alkyl or a para-fluoro...but it can't have both.  I assume you mean 4-fluoro-aminorex.



Sorry, not thinking, para-fluoro amino rex.


----------



## Dr.Heckyll

morninggloryseed said:
			
		

> 4-MAR is 4-Methyl-Aminorex.  What do you mean "plain MAR"?  Do you mean Aminorex without the para-methyl?
> 
> With that in mind, there can be no such thing as "pFMAR" as aminorex can either have an para-alkyl or a para-fluoro...but it can't have both.  I assume you mean 4-fluoro-aminorex.



The 4-methyl is on the oxazoline ring, not the phenyl. 4-Methylaminorex is the compound also known as U4EA. So there could welll be a 4'-methyl on tge phenyl ring. This would then be 4,4'-dimethylaminorex. The para-flouro compound would then be 4'-fluoro-4-methylaminorex.


----------



## fastandbulbous

haribo1 said:
			
		

> I know this sounds dumb, but I REALLY enjoyed 4MAR but plain MAR is supposed to be about 4 times more potent. The strongest of the series (ED50) was the 4-fluoro. Now, I know 4-F amphetamine isn't quite as speedy but a bit more happy. Wouldn't pFMAR be worth giving the once over? That or possibly a pseudohalogen?



I know somebody who synthed para-fluoro-4-MAR & he said the first time it had entactogen like properties, but subsequent doses just became unpleasantly stimulating (more psychosis & less fun), so all in all I don't think it's be worth the bother




> Now you need to reduce the ketone to the alcohol, prepare the acetate, separate the isomers, and you get the well known stimulant levophacetoperane, which is sort of the reverse ester of methylphenidate.



No, just leave it as the keto group - if you reduce the ket group of pyrovalerone you don't retain the dopamine reuptake properties, so it's probably be best to leave the keto group untouched here as well


----------



## MDPVagrant

fastandbulbous said:
			
		

> I know somebody who synthed para-fluoro-4-MAR & he said the first time it had entactogen like properties, but subsequent doses just became unpleasantly stimulating (more psychosis & less fun), so all in all I don't think it's be worth the bother


Fwiw, people who rave about entactogenic properties tend to dislike straight-up stimulants... so what this person said may not be valid for those of us who DO enjoy "plain stimulation."  In other words, it may be worth the bother.


----------



## fastandbulbous

^ No he's the same one who synthed a series of alpha-amino alkanones & had a liking for plain out & out stimulants as well (he really rated 1-phenyl--2-(N-methylamino)-1-butanone and ended up consuming quite a bit of the stuff) - he said that it simply wasn't too pleasant after the initial experience with it. Strangely he never got around to synthing the methylenedioxy analogue of 4-MAR, which I had a feeling would have been a definite entactogen considering all the aminorex derivatives are effctively N-methyl derivatives, with the methyl group also attached to the beta-substituted oxygen, which also tend to retain entactogen activity (_a la_ methylone).

As regards pure stimulants, I was always under the impression that the meta-fluoro substituted compounds were the best of the bunch, not the para-substituted (ie that 3-fluoroamphetamine is a much better stimulant than 4-fluoroamphetamine). I may be wrong though (my memory has bloody big holes in it due to moments of excessive drug intake - not quite Swiss cheese, but not watertight either! )


----------



## fastandbulbous

Dr.Heckyll said:
			
		

> Yes, in France as lidepran (http://www.psychotropics.dk/usr_vie...lphabetical+index&historyline=&Catalogtype=A), and it's a UN scheduled substance.



So it's listed in the UN psychotropic drugs document? That seems strange as it's not controlled in the UK or anywhere in Europe AFAIK, yet anything on the UN document is normally automatically added to the list of controlled substances in the EU (hence the fate of 2C-I, 2C-T-7 & TMA-2)


----------



## Helios.

Butthead thinks fluorine sucks at making these compounds better.


----------



## hussness

How does levophacetoperane compare to methylphenidate in potency, side effects, anything else?


----------



## fastandbulbous

^ Nigh on identical


----------



## haribo1

*1-phenyl-2-(N-methylamino) butane*

F&B. I know a Dutch chap who made the 1-phenyl-2-(N-methylamino) butane & optically purified it. He also made methamphetamine & optically purified that. He reckoned that the butane analog was BETTER than the propane version. His explanation was that it crossed the BBB better (or something). It's a shame because he was a 'problem user' i.e. he suffered mental illness due to excessive stimulant abuse. He truly believed that there was a worldwide conspiricy against him and EVERYONE was involved. He said he was still friends with me because he thought I was a 5th columnist of the 'company' who had a soft spot for him and was putting in good words to keep him out of trouble. I flipped. I figured if/when something bad happened, he would believe I had let him down or worse, grassed him up!
 Anyway, back to the plot. What does that 1-one do to the binding? I was told by people that methcathinone was inferior to methamphetamine but methylone is very similar indeed to MDMA but what about things like MDPV (or 3,4 dichloro PV for that matter). Are the amines as well as the amino ketones active? If the butanones are active, then while MBDB is controlled, 3,4 methylenedioxy 5 methoxy WOULD be legal in the UK AFAIK? I quite liked it when I tried the 3 carbon primary version.


----------



## fastandbulbous

Yeah, I know someone who produced a whole series of alkanone derivatives and his favourite was 1-phenyl-2-methylamino-1-butanone. I think it's that it has a small amount of noradrenergic activity coupled with a lot of dopaminergic activity, which seems to be the right combination for maximum euphoric effects


----------



## Xorkoth

> I was told by people that methcathinone was inferior to methamphetamine but methylone is very similar indeed to MDMA



Methcathinone is definitely very inferior to methamphetamine.  In fact, it downright sucks (in my experience).


----------



## hussness

fastandbulbous said:
			
		

> Yeah, I know someone who produced a whole series of alkanone derivatives and his favourite was 1-phenyl-2-methylamino-1-butanone. I think it's that it has a small amount of noradrenergic activity coupled with a lot of dopaminergic activity, which seems to be the right combination for maximum euphoric effects



Of this series which stereochemical configuration about the alpha-alkyl corresponds to the more active enantiomer?  Do they happen to follow the configurational rules for amphetamine (even though they probably don't share a similar mechanism)?


----------



## haribo1

hussness said:
			
		

> Of this series which stereochemical configuration about the alpha-alkyl corresponds to the more active enantiomer?  Do they happen to follow the configurational rules for amphetamine (even though they probably don't share a similar mechanism)?



That is a VERY good point. What isomer of MBDV was more active? This 1-one thing is becoming more and more fascinating. I always assumed that ring-substitution was required to make the PEAs dopamagenic but it seems not. That would certainly be interesting from a CsA POV. It LOOKS like one drug but ACTS like another. Like FSDoA pointed out about bemigride; looks like a barb but its a stim, not a downer...In fact, has anyone considered bemigride analogs?






And this, I believe, is the strongest substitution pattern for a barb






Maybe its worth trying? I do suspect its a general CNS stimulant so nothing 'nice' but who can say...


----------



## fastandbulbous

In fact, has anyone considered bemigride analogs?

http://pubchem.ncbi.nlm.nih.gov/imag....fcgi?cid=2310



> And this, I believe, is the strongest substitution pattern for a barb
> 
> 
> 
> Maybe its worth trying? I do suspect its a general CNS stimulant so nothing 'nice' but who can say...



Like a general CNS convulsant trigger - that's especially true of drugs based on the barbiturate structure


----------



## hussness

Going further with the SARs of cathinone analogs does annulation of the nitrogen (like with MDPV) really do anything significant to alter the properties of the drug?


----------



## fastandbulbous

Well there's a German patent for it as an appetite supressant (somewhere in Chemical Abstracts - don't ask I can't remember) and it's a better stimulant than diethylpropion, with less side effects, but beyond that there's nothing that major to recommend it - with the beta ketones the CNS stimulant activity incresaes with chain length, reaching a max with the hexanone derivatives then tailing off quite sharply


----------



## Dondante

How about a muscarinic agonist like arecoline?


----------



## mad_scientist

Dondante said:
			
		

> How about a muscarinic agonist like arecoline?



Arecoline mostly just makes you sweat, you get a little bit wired but its more like nicotine than anything else. Tried both fresh betel nuts and concentrated extract, the extract is stronger but they both taste nasty and don't do that much. 

Strangely enough though betel is one of the most widely used drugs in the world on a population basis, literally hundreds of millions of people in south east asia chew betel nuts every day, but you hardly even hear about it in western countries. I guess arecoline must be fairly addictive when its used regularly but in my experience there wasn't really any high to speak of.


----------



## kong

Some of the guys my dad used to work with chewed betal nuts.  I tried some and was also not impressed, although the nuts were somewhat stimulating similar to caffiene, but it felt to jittery for me to enjoy it.  I can see how people might become addicted however.


----------



## fastandbulbous

hussness said:
			
		

> Of this series which stereochemical configuration about the alpha-alkyl corresponds to the more active enantiomer?  Do they happen to follow the configurational rules for amphetamine (even though they probably don't share a similar mechanism)?



Not a clue as he only produced the racaemic versions, but I have more than a sneaking feeling that the most active isomer has the same absolute configureation as the amphetamines (well ir's true for cathinone/methcathinone so I'd imagine it's that way for the larger alpha alkyl chains)




> Arecoline mostly just makes you sweat, you get a little bit wired but its more like nicotine than anything else. Tried both fresh betel nuts and concentrated extract, the extract is stronger but they both taste nasty and don't do that much.




Betel nut is possibly one of the vilest tasting plant materials I've ever decided to chew on and I can't imagine how it became so popular as I can't imagine ever getting to like the taste. Khat is an acquired taste, but once you're used to it the taste almost becomes part of what you look forward to (almost!)


----------



## Dr.Heckyll

How about 4-benzylpiperidine? According to US patent 3632767 it's an antidepressant at low doses and a stimulant at higher doses. Conveniently, it's commercialy available from a number of chemicals supply houses.


----------



## fastandbulbous

^ So is 4-(alpha,alpha-diphenylmethyl)piperidine (or is it pyridine) - it's a reuptake inhibitor. Low doses are probably similar to what amineptine would be like as it's (amineptine) apparently a specific dopamine reuptake inhibitor.

Only thing that preys on my mind is if it's such a versitile drug, why hasn't some firm marketed it as a clinical antidepressant? I know it's most probably because of an abuse potential, but it would be nice to see that confirmed in writing just in case it's something nasty like what happened with alphaethyltryptamine (fatal agranulocytosis)


----------



## Dr.Heckyll

Aletamine derivatives according to J. Med. Chem.; 1972; 15(6); 590-592 could also be considered interesting:


> However, all of the compounds, unlike aletamine, showed
> CNS stimulation as indicated by hyperreflexia, irritability,
> and increase in spontaneous motor activity. In particular,
> 19 and 21, which were further examined in chloral hydrate
> antagonism (Table V), approximated the stimulating effect
> of d-amphetamine.


----------



## hugo24

Care to share what the structures of 19 and 21 are?The simple aletamine seems mainly a analgetic.

Clinical Evaluation of Aletamine as an Analgesic 
Leo J. Cass M.D.1 and Willem S. Frederik M.D., Ph.D.2 
1 University Health Services, Harvard University, Cambridge, Mass., and Visiting Physician, Long Island Hospital, Boston, Mass.
2 University Health Services, Harvard University, Cambridge, Mass.



The analgesic potency of aletamine hydrochloride was investigated in a doubleblind cross-over study with 35 patients. Aletamine hydrochloride was utilized at two dosage levels (250 and 125 mg. three times a day) and was compared with propoxyphene hydrochloride (65 mg. three times a day) and a placebo. Patients were evaluated three times a day, one hour after administration for relief of pain and once each day for changes in mood. Side effects observed or spontaneously expressed by the patients were also recorded.

The results of this study indicate that, given three times daily, aletamine hydrochloride, 250 mg., has a greater analgesic potency than propoxyphene hydrochloride, 65 mg., or aletamine hydrochloride, 125 mg. Aletamine hydrochloride, 125 mg., produces an analgesic effect almost equivalent to that of propoxyphene hydrochloride, 65 mg. Only minor changes in mood were evident for any of the treatments. The incidence of side effects was relatively low for each of the four drug regimens


http://jcp.sagepub.com/cgi/content/abstract/6/2/96


----------



## Dr.Heckyll

Here they are:


----------



## Dr.Heckyll

I'll throw in another one, just to keep the discussion alive: how about dimethocaine? Only slightly less potent than cocaine according to one source: http://www.ncbi.nlm.nih.gov/entrez/...t_uids=7635175&query_hl=1&itool=pubmed_docsum


----------



## fastandbulbous

To bypass the stress of attempting to find it's structure using Google (all dead ends unless you want to cough up god knows how much for the full paper), I eventually found a site that didn't treat it's molecular structure like it was how to turn lead into gold, I've stuck a pic below.

What got me is that it's an ester of para-aminobenzoic acid, and not even a very complicated one at that. If it's all that's being hinted at I'm very surprised that it's not flooding the streets as we speak (or even earlier)


----------



## phase_dancer

Shit, I could have posted it. It's on the CD version of 13th ed Merck index. Wouldn't be hard to synthesize (we did very similar things in second year org chem) so I tend to agree that it's rather surprising it's not heard about on the streets.


----------



## hugo24

And who says this is a good stimulant in humans?


----------



## MattPsy

From PubMed: "Cocaine and dimethocaine produced similar 12-fold increases in dialysate dopamine at concentrations of 0.1 mM and 1 mM respectively."


----------



## mad_scientist

fastandbulbous said:
			
		

> To bypass the stress of attempting to find it's structure using Google.....



Pubchem has structures for pretty much any compound that has a CAS number and a good few that don't.

This site is pretty good for finding structures of obscure compounds, and if you click on the structure it goes to the pubchem page for that molecule:

http://www.chemindustry.com/apps/chemicals


----------



## haribo1

fastandbulbous said:
			
		

> To bypass the stress of attempting to find it's structure using Google (all dead ends unless you want to cough up god knows how much for the full paper), I eventually found a site that didn't treat it's molecular structure like it was how to turn lead into gold, I've stuck a pic below.
> 
> What got me is that it's an ester of para-aminobenzoic acid, and not even a very complicated one at that. If it's all that's being hinted at I'm very surprised that it's not flooding the streets as we speak (or even earlier)



That structure is very close to some of the local anathetics. I've heard that shooting those local anasthetics gives a rush but no high. Maybe these modifications give the the rush AND the high. I mean, can you freebase tetracaine?


----------



## hussness

what kind of therapeutic range does dimethocaine have?  Given that it substitutes for cocaine at 10x the dose, what kind of "recreational ratio" would it have?


----------



## haribo1

fastandbulbous said:
			
		

> Yeah, I know someone who produced a whole series of alkanone derivatives and his favourite was 1-phenyl-2-methylamino-1-butanone. I think it's that it has a small amount of noradrenergic activity coupled with a lot of dopaminergic activity, which seems to be the right combination for maximum euphoric effects



I wonder about para fluoro aminorex. It's supposed to be the most euphoric of the lot, isn't it (as well as the strongest of the series). Precursors no problem. Should do the 1-pot shot and freebase is smokable...


----------



## Vanadium

here's an idea of MDPV analaog : 1,4-dimethoxy instead of methylenedioxy group


----------



## Morninggloryseed

I am pretty sure tetracaine is a stimulant.  I remember a couple of newsprograms about it in the late 80s...some doctors in NYC were giving it as a gel, up the nose on a q-tip, as some form of therapy.  The newsreporter (undercover) was shown with q-tips up his nose claiming to feel well-being and other stimulant effects.


----------



## haribo1

I think tetracaine might give a high by itself and this interesting analog posted by F&B makes me think this even more.






This could be the new crack... An easy to make crack alternative that doesn't show up in tests & since it's lower cost, would make importation costs reduce. Price goes through floor, SA dealers screwed. The new 'mom n' pop meth-labs' out of fashion. Start hoarding precursors...


----------



## Jamshyd

Vanadium said:
			
		

> here's an idea of MDPV analaog : 1,4-dimethoxy instead of methylenedioxy group



I doubt this will do what you may be expecting it to do, just like the methylenedioxy counterpart didn't do what many people here hoped it would do.

It looks like the bulkines added to the chain renders it useless for amphetamine-like suggestions. 

EDIT: RE tetracaine... interesting, I thought I saw it OTC the other day. And indeed, look:



> In Canada-
> 
> * After Burn Double Strength Gel 5
> * After Burn Double Strength Spray 5
> * After Burn Gel 5
> * After Burn Spray 5
> * Alphacaine 5
> * Dermoplast 2
> * Endocaine 1
> * Norwood Sunburn Spray 5
> * Nupercainal Ointment 4
> * Pramegel 7
> * Shield Burnasept Spray 1
> * Tronothane 6
> * Xylocaine 5


----------



## haribo1

Dear Jamshyd,
                       You can sell all this for cash. From a fake address (for security) and cash only (no banks).

S-)


----------



## nuke

Be careful, tetracaine is an MAOI too.



> Differential effect of tetracaine and bupivacaine on catecholamine and 5-hydroxytryptamine turnover.
> Rosenberg PH, Nissinen E, Mannisto PT, Tuomisto L, Heavner JE.
> 
> The effect of the local anesthetics, tetracaine and bupivacaine, on monoamine oxidase (MAO) activity of rat brain and on the major steps of catecholamine and 5-hydroxytryptamine (5-HT) turnover was examined. The IC50 of tetracaine for MAO-A and MAO-B inhibition was 1.2 microM and 19.5 microM, respectively. Up to 2.5 mM bupivacaine was without effect on either form of MAO. None of the following activities in rat brain or adrenal medulla were inhibited by 5-2500 microM of tetracaine or bupivacaine: catecholamine-O-methyltransferase, tyrosine hydroxylase, dopamine-beta-hydroxylase. Tetracaine caused only a moderately potent inhibition of synaptosomal uptake of norepinephrine (NE) (IC50 14 microM), dopamine (IC50 37 microM) and 5-HT (IC50 45 microM). The potent and specific MAO inhibition by tetracaine, in association with an impaired uptake of synaptosomal amines, may lead to an increase in the synaptosomal content of neurotransmitter amines, such as 5-HT and NE, with possible antinociceptive consequences.



And rhesus monkeys don't like it:


> On the relationship between the dopamine transporter and the reinforcing effects of local anesthetics in rhesus monkeys: practical and theoretical concerns.
> Wilcox KM, Rowlett JK, Paul IA, Ordway GA, Woolverton WL.
> 
> Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA.
> 
> RATIONALE: Drugs that are self-administered appear to vary in their potency and effectiveness as positive reinforcers. Understanding mechanisms that determine relative effectiveness of drugs as reinforcers will enhance our understanding of drug abuse. OBJECTIVES: The hypothesis of the present study was that differences among dopamine transporter (DAT) ligands in potency and effectiveness as a positive reinforcers were related to potency and effectiveness as DA uptake inhibitors. Accordingly, self-administration of a group of local anesthetics that are DAT ligands was compared to their effects as DA uptake blockers in vitro in brain tissue. METHODS: Rhesus monkeys were allowed to self-administer cocaine and other local anesthetics i.v. under a progressive-ratio schedule. The same compounds were compared in standard in vitro DA uptake assays using monkey caudate tissue. RESULTS: The rank order of both potency and effectiveness as reinforcers was cocaine > dimethocaine > procaine > chloroprocaine. Tetracaine did not maintain self-administration. For inhibiting DA uptake, the potency order was cocaine > dimethocaine > tetracaine > procaine > chloro-procaine. At maximum, these compounds were equally effective in blocking DA uptake. Lidocaine did not inhibit DA uptake. CONCLUSIONS: The potency of local anesthetics as positive reinforcers is likely related to their potency as DA uptake inhibitors. Variation in their effectiveness as positive reinforcers was not a function of differences in effectiveness as DA uptake blockers, but may be related to relative potency over the concentrations that are achieved in vivo. Effects at sodium channels may limit the reinforcing effects of local anesthetics.



Dimethocaine is probably the best bet..


----------



## fastandbulbous

> Be careful, tetracaine is an MAOI too.



Even more important & what everyone seemd to have missed is that local anaesthetics bugger the propagation of the synchronizing signal from the sino-arterial node across heart muscle tissue. They may be good dopamine reuptake inhibitors, but if there better at being local anaesthetics (bit rusty on this - they inhibit Na/K ATPase?) it's not going to take much above a theraputic dose for the user to be fucked in a way he never even considered. Add to that the propensity of the prototype stimulant for these drugs to, er, cause users to get a bit carried away with repeated/increased dosages and we have the most rabid anti-drugs campaigners vison come true. A cocaine analogue equivalent to 3-methylfentanyl in the 'drug serial killer' stakes. You can't even depend upon examples from clinical use of the drug, as then it's not IVed, it's IMed and with a vasoconstrictoe like adrenaline thrown in with it to massively slow the diffusion of the drug from the tissues into the main blood circulation

All potentially very nasty


----------



## hussness

^This was a more articulate way of saying what I was trying to ask.


----------



## mind

what about the methamphetamine version of 4-fluoroamphetamine (4-fluoro-methamphetamine)?
can't find any info about it.


----------



## vecktor

mind said:
			
		

> what about the methamphetamine version of 4-fmp?
> can't find any info about it.



4-fmp?


----------



## vecktor

I believe the n-methyl analogue of 4 fluoro amphetamine was discussed in an earlier thread.

 I don't see the logic of coding it as 4-FMP,  when the standard coding for the chloro or methoxy analogue has always been PCA  (Para Chloro Amphetamine)or PMA.

The 3 fluoro isomer appears much more intersting anyways.

there are some patents relating to the fluoroamphetamines and if I can dig up the reference I'll post it, I would be very suprised if the N-metyl cogener hadn't been investigated.


----------



## Jamshyd

I found 4-FA to be as peripherally stimulating as ephedrine.

It is also definitely NOT what you'd look for in a stimulant - it is more like MDMA in its "stimulating" effects (ie. stupefying, scattered, lethargic). 

I have no reason to think that 4-FMA would be better.

(And I prefer using the acronyms 4-FA or PFA over "4-FMP")


----------



## mind

sorry 4-fmp is used as "slang" for 4-fluoro-amphetamine. can understand the confusion, i have already edited my original post for more clarity.

Bandil (from the bee site) tried to synth it, but it didn't want to form crystals iirc.


----------



## Jamshyd

^ Didn't this person also claim to have synthed 4-Bromomethcathinone, and claimed it produced a +++?


----------



## haribo1

Bandil is usally a reliable source


----------



## Helios.

Barricuda1965?


----------



## Helios.

4-Cl-methamphetamine > 4-F-amphetamine.
where > means "greater than" or "better than"


----------



## nuke

I bet 3,4-dichloro-methamphetamine is the best, but there's way too much in studies pointing to neurotoxicity for the two (unless you don't mind that, I guess, some people smoke meth all day!)


----------



## Helios.

*superpowers*

You're right, I don't mind.
I am more than willing to try both 4-Cl-METH and 3,4-di-Cl-METH.
You could give me some if you wanted.

back on topic,
Stimulant of the Future:
2-Bz-2-(CO2CH3)-piperidine HCl.


----------



## mind

The most potent "neurotoxins" are the 4- Bromo- or 4-Chloro-amphetamine and methamphetamine derivatives.

http://www.maps.org/pipermail/maps_forum/2003-February/005315.html


----------



## haribo1

So, dimethocaine has been shown to displace cocaine off it's receptors, in fact, in tests on monkeys, in fact, the self-administered monkeys got 0.1-0.3mg/Kg iv OR 0.030 to 0.17 dimethocaine. That makes it's DAT binding 2-3 times that of cocaine. Wonder if adding an alkyl group to that para amino (like tetracaine) would make it stronger again?
 The thing to remember F&B is that your average dealer knows nothing of new chemicals. If they knew it worked, they would be cutting our coke with it right now! MDPV isn't shifting mountains because it's an acquired taste requiring that most had to come by in drug circles 'moderation'.

Quote: This data demonstrate the locomotor stimulant, reinforcing and anxiogenic actions of dimethocaine similar to those reported for cocaine in animals. In addition, these findings support a role for dopaminergic activity, rather than local anesthetic action, in the behavioral effects caused by dimethocaine.


----------



## haribo1

Vanadium said:
			
		

> here's an idea of MDPV analaog : 1,4-dimethoxy instead of methylenedioxy group



Isn't that 2,5?


----------



## Helios.

Yes.

back on topic:

2,4-dimethoxymethamphetamine HCl.


----------



## Jamshyd

^ I'd be surprised if this one isn't in PiHKAL. Wouldn't that be DMMA or something? Too lazy to look it up  

In any case, shulgin does observe that alkylating the nitrogen in ring-substituted amphetamines renders the drug practically useless (or lowers potency at best).


----------



## Helios.

The N-desmethyl version of 2,4-dimethoxymethamphetamine is in PiHKAL, but 
N-methylation does not affect the 3,4's the 3's or the 4's although it does disenable the 3,4,5's and the 2,4,5's.

got it?
great !!!


----------



## Helios.

benzylic cyclohexyl methamphetamine hydrochloride.


----------



## Helios.

piperonylic cyclohexyl methamphetamine hydrochloride.


----------



## Helios.

2-chlorophenylic cyclohexyl methamphetamine hydrochloride.


----------



## Helios.

1-phenyl-1-(2-piperidinyl)-cyclohexane hydrochloride.


----------



## Helios.

*repost*

benzylic cyclohexyl methamphetamine hydrochloride.


----------



## haribo1

fastandbulbous said:
			
		

> Yeah, I know someone who produced a whole series of alkanone derivatives and his favourite was 1-phenyl-2-methylamino-1-butanone. I think it's that it has a small amount of noradrenergic activity coupled with a lot of dopaminergic activity, which seems to be the right combination for maximum euphoric effects



So, the 3 carbom (methcathinone) is 'crap' but the 4-chain analogue is good?


----------



## fastandbulbous

Helios. said:
			
		

> benzylic cyclohexyl methamphetamine hydrochloride.




Did you like the taste of the gag before? So much that you're eager to have it returned? Then don't start with the vague multiple posts - one would have sufficed and it didn't need that repost.

Got me?


----------



## fastandbulbous

haribo1 said:
			
		

> So, the 3 carbom (methcathinone) is 'crap' but the 4-chain analogue is good?



Yeah, apparently the degree of dopaminergic reuptake inhibiton increases with chain length up to a 6 carbon chain - thing is the effects on the noradrenergic system go down with increasing chain length (which is why MDPV is almost exclusively dopaminergic in action). If you want euphoria as opposed to something for attention/focus control, you need some adrenergic activity


----------



## Helios.

Hence, N,alpha-dimethyl-PEAs are the most worthy.


----------



## ebola?

>>Got me?>>

No...I can only think of a squid eating dough in a polyethylene bag.

ebola


----------



## Helios.

I just lapped you all.


----------



## haribo1

fastandbulbous said:
			
		

> Yeah, apparently the degree of dopaminergic reuptake inhibiton increases with chain length up to a 6 carbon chain - thing is the effects on the noradrenergic system go down with increasing chain length (which is why MDPV is almost exclusively dopaminergic in action). If you want euphoria as opposed to something for attention/focus control, you need some adrenergic activity



Wow, so it's a 1-pot thing to make from propio butiophenone, bromine, methyl amine and some solvents. It would be legal in the UK as well. Whats the dosage?


----------



## fastandbulbous

About 10-20mg for 1-phenyl-2-(N-methylamino)-1-butanone - that's from memory. Give me a mo and I'll have a rummage and see if I can verify that .

I do remember that it seems to have the right dopaminergic/noradrenergic activity to produce a reasonable amount of euphoria - a lot better than methcathinone, which I've found can leave you feeling a bit 'jittery' (I'd guess down to adrenergic activity). Of course if you bung a meyhtylenedioxy ring onto it, you still end up with an entactogenic like activity. That's quite unlike the 5 carbon valerophenones that disp;lay almost no such erffects (MDPV causes some colour brightening.enhancement with higher doses, but very little else).

The pyrrolidine version of the butyrophenone didn't get made (or I wasn't informed or have forgotten) so I don't know quite what that would be like; mind you, the pyrrolidine version of the propiophenone (like a cyclicized version of diethylpropion) is a more potent CNS stimulant compared with diethylpropion for the same amount of anorectic activity (German patent in Chem Abstracts) which is most [robably why it was rejected in favour of diethylpropion for the final product. That sort of implies that 1-phenyl-2-(1-pyrrolidyl)-1-butanone might be the one to go for

In the end you can only apply the 'suck it and see' test for final assessment


----------



## hugo24

"Of course if you bung a meyhtylenedioxy ring onto it, you still end up with an entactogenic like activity."


That would be the Mebylone.


----------



## Helios.

What's wrong with clean burning non-ketonic propane?


----------



## hugo24

I must say I liked Methcathinon,only second to meth.Altough it has more of the manic repetitive stuff when going higher with doses (repeated).
But on some level I think it has emphatogenic/"window opening" qualities,probably serotonergic in nature,at least it felt a bit like MDMA when I tried 50mg Methcathinon orally,only without the visuals.

If the butyrophenon analog is even better,well...


----------



## fastandbulbous

Actually, today I got to play around with 2-(_alpha,alpha_-diphenylmethyl)piperidine - the one Shulgin mentions in 'Future Drugs of Abuse' as possibly being as potent as methamphetamine. Well yes & no; yes it's a strong locomotor stimulant with a long action, but no, it's not as euphoric as meth and has virtually no peripheral symptoms such as raised heart rate, sweating or dry mouth. As I mentioned to someone, 5mg had me marching around like I was ready to invade Poland  , but it's difficult to gauge quite where your head is at because of the lack of peripheral symptoms to use as a measuring stick. It has a very, very clean  feeling with a very positive feeling of being able to focus on a task (it's a dopamine reuptake inhibitor) and of having a lot of useable energy; the one thing that seems totally absent though is the effect on libido that say meth or MDPV has (which isn't a bad thing as it's difficult to not get distracted by all things sexual these days with MDPV).

I may write a report on iy, or leave it for a few days until I can beter get a measure of the stuff (who am I kidding, I feel like doing things like it's the first day of spring at the moment!). I'd say that Shulgin wasn't too wide of the mark with this stuff,


PS So far I've had it referred to as 2-DPMP, but for a roll of the tounge name, I like desoxypipradrol (desoxy meaning having an oxygen atom removed, the same way methamphetamine used to be referred to as desoxyephedrine).


----------



## vecktor

was it 2-(_alpha,alpha_-diphenylmethyl)piperidine which was discontinued in studies due to the extreme variation in individual sensitivity to the compound which appeared in trials: shaking etc at low doses? 

there are a couple of interesting dopamine reuptake inhibitors which are based on the related pyridine rather than the piperidine, for example 4-(alpha alpha diphenylmethyl) pyridine is equipotent with cocaine, it also appears that the 2 pyridine is also an active stimulant. all of these substances are commercially available, though I have no idea what they are used for.

This sort of leads into the lefetamine discussion elsewhere as replacing one phenyl with a benzyl group in both of the above compounds leads to an active DAT and NE reuptake inhibitor in a way a distant analog of lefetamine.

I believe that 4-benzyl pyridine or was it the piperidine has come up in discussion, it appears that 4 benzyl pyridine is almost inactive as a DAT inhibitor.

methyl 3-phenyl-norbornane-2-carboxylate might be an interesting substance, a non nitrogenous analogue of the great substance fencamfamine.. it fits with the SAR for DAT inhibitors. though the methyl ester might have to be replaced with a terminal amino alcohol to increase water solubility.


----------



## hugo24

Doesent sound like its non-euphoric,first day of spring,my dear...We just got 20cm of snow...


----------



## fastandbulbous

Actually the '1st day if spring' quip was just that it was very nice to find a CNS stimulant that doesn't leave me feeling like I've got a bit too much adrenaline in my bloodstream. Just looking at vecktors post, it mentions the (adopt Edinburgh schoolmistress voice) _creme de la creme _stimulant IMO, fencamfamine. That was so smooth it was the James Bond of stimulannts!


Oh, one other thing I like about it (desoxypipradrol), it has bog all anorectic effect, which means I can have my cake and eat it! (as opposed to looking at it, feeling a bit sick and saying I might try a bit later...  )


----------



## vecktor

fencamfamine is very very pleasant, it seems to have the right amount of releasing versus reuptake action on the right neurotransmitters...salivating now

other fencamfamine analogs include the N-methyl analogue, the N-propyl analogue, the 2' hydroxyphenyl analogue etc etc. whilst at first sight the nornbornane appears complex to synthesise and there is the obvious problem of multiple isomers, diels adler is a great reaction and a good use of those pesky itchy nitrostyrenes.

the original merck patent deals with the nn dimethylamino the n-methyl etc 
patent GB 913866

a word of warnng, I have made the mistake of misordering fencamine which whilst a stimulant is totally unrelated.


----------



## Survival0200

If fencamfamine (fencamfamin according to DEA) is so good, why isn't it more popular? Why isn't it more abused? Why is it only C-IV? 

Are we talking about the stuff, that is sold/has been sold under the name Reactivan?


----------



## vecktor

Survival0200 said:
			
		

> If fencamfamine (fencamfamin according to DEA) is so good, why isn't it more popular? Why isn't it more abused? Why is it only C-IV?
> 
> Are we talking about the stuff, that is sold/has been sold under the name Reactivan?



because cocaine is more readily available?
because the average muppet meth or MDMA chemist would struggle with the synthesis? who knows.

In the UK at least it is very rarely prescribed and is a controlled drug

Reactivan is a merck trade name for low dose fencamfamine 10mg per tablet plus vitamins.

there are several drugs out there which are inexplicably unpopular, despite being rather tasty.

now I shall ask ze questions..

what does flushed  tomato smiley mean?


----------



## hussness

While we are on the subject of fencamfamine derivatives, does anyone know anything about the 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane dopamine uptake inhibitors, most recently cited in this article:

J. Med. Chem., 42 (5), 882 -895, 1999.


----------



## vecktor

hussness said:
			
		

> While we are on the subject of fencamfamine derivatives, does anyone know anything about the 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane dopamine uptake inhibitors, most recently cited in this article:
> 
> J. Med. Chem., 42 (5), 882 -895, 1999.



 there is a thesis related to the J med chem article here:

http://etd.gatech.edu/theses/available/etd-06242004-225750/unrestricted/moore_susanna_200406_phd.pdf


----------



## fastandbulbous

> a word of warnng, I have made the mistake of misordering fencamine which whilst a stimulant is totally unrelated.



Well I actually ordered fencamfamine (in the days when Aldrich still dealt eith me) & just before it was readded to thre Misuse of Drugs Act, had a couple of policemen come round to remind me of it's changing status & the need to dispose of it as I didn't have a Home Office licence. Guess how it was disposed of? - That was a rather good Xmas as I recall!

I have no idea why it never caught the imagination of the drug using community as the people who got to try some thought it was infinitely better than amphetamine's rough & ready feel


----------



## Jamshyd

If I remember correctly, Fencamfamine is Sch. 1 in Canada, along with Cocaine and all Opiates. The same schedule contains PCP, a couple of obsecure benzos (definitely brow-raising) and a few barbiturates.  

Canadian schedules are very weird. It seems like they are organized roughly according to drug category (rather than claimed medical usefulness as with the US). Sch.2 is entirely devoted to cannabinoids. Sch. 3 seems to comprise most tryptamines and phenethylamines/amphetamines, and I think Ketamine. Sch. 4 is mostly benzos and the rest of the barbs and depressants. The lower schedules deal with precursors and steroids. 

EDIT: nevermind, I actually mixed up Fencamfamine's and Ketamine's scheuling. It is actually the former is Sch. 4 and the latter is Sch. 1 as a sub-article of PCP. How nauseating.

EDIT2: Hahaha. I just came across this article randomly while skittering through the CDSA trying to figure out the rationalle. 



> [pertaining to benzodiazepines in pariticular] (3)  A targeted substance [viz. benzos] that constitutes the remainder of an open ampule, the partial contents of which have been administered to a patient, may be destroyed by a hospital employee who is a licensed health professional without a witness.



I love the fact that it "may" be "destroyed" _without_ a witness. So I guess if you're a doctor, you can always give half-assed shots of benzos to patients and "destroy" the rest with your liver . Sorry to go off topic but I find this ammusing.


----------



## shvender hoot

What about a stimulant that works as an antagonist at melatonin receptors? I don't think that there are any that has such a particular mode of action.


----------



## fastandbulbous

vecktor said:
			
		

> there is a thesis related to the J med chem article here:
> 
> http://etd.gatech.edu/theses/available/etd-06242004-225750/unrestricted/moore_susanna_200406_phd.pdf



Had a read through tyhat last night & it was very interesting, a lot of the compounds didn't have the usual Aryl-C-C-N structure as their basis. Also had a bit about the postulated pharmacophore for the DAT binding site. Lots of food for thought. It does seem that if you want to design a really good dopamine reuptake inhibitor, it's a def advantage to have a conformationally restricted structure to stick your other bits on to (that's real SAR-design talk for you!); generally formed by joining together two ring structures eg tropane or norborane.

Does make the synthetic chemistry involved a bit of a pain in the arse unless you've got something useful like diels-alder additions to play around with. I'm Surprised that they haven't also had a bit play around with the adamantane structure in the hunt for something to act as a methadone equivalent for cocaine addiction (or maybe they have - it's quite a while since I've been in a university library), as it's rigid enough and I believe 1-adamantanamine has dopaminergic activity.


----------



## vecktor

fastandbulbous said:
			
		

> Had a read through tyhat last night & it was very interesting, a lot of the compounds didn't have the usual Aryl-C-C-N structure as their basis. Also had a bit about the postulated pharmacophore for the DAT binding site. Lots of food for thought. It does seem that if you want to design a really good dopamine reuptake inhibitor, it's a def advantage to have a conformationally restricted structure to stick your other bits on to (that's real SAR-design talk for you!); generally formed by joining together two ring structures eg tropane or norborane.
> 
> Does make the synthetic chemistry involved a bit of a pain in the arse unless you've got something useful like diels-alder additions to play around with. I'm Surprised that they haven't also had a bit play around with the adamantane structure in the hunt for something to act as a methadone equivalent for cocaine addiction (or maybe they have - it's quite a while since I've been in a university library), as it's rigid enough and I believe 1-adamantanamine has dopaminergic activity.



If I can find it I will post a link to an indian thesis which is most concerned with some seriously cool chemistry but as an aside mentions forward and back bridged cocaine or rather WIN analogues imagine a bridge fron the tropane N to the carboxylic ester position or to the other ring the forward bridged compounds are potent DAT inhibitors, if it is not online anymore I will have to find somewhere to post it and link to there. there is certainly potential for a forward bridged fencamfamine analog.

I am very interested in fencamfamine, 1  because it is nice and 2 because it is a substrate type releaser as well as a reuptake inhibitor and there is potential to modify the Dopamine, Serotonin, norepinephrine ratio.


----------



## vecktor

http://dspace.ncl.res.in/dspace/bitstream/2048/14/1/th1280.pdf

tricyclic WIN analogs.


----------



## vecktor

shvender hoot said:
			
		

> What about a stimulant that works as an antagonist at melatonin receptors? I don't think that there are any that has such a particular mode of action.



for a minute I thought you said melanocortin which is interesting rather than melatonin which doesn't seem to be.
I suspect that partial agonists or antagonist of melatonin will mildly mess with the circadian rhythem and not a lot else,
the abstrat is ere
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=10350542&dopt=Abstract


----------



## fastandbulbous

^ Yeah, I was thinking that - melatonin has very little to do with motivation or reward pathways, which is what makes the previously discussed drugs so interesting. As vecktor said, they'd just chance to fuck up the circadian rhythm, meaning that you'd get disturbed levels of things like cortisol etc that are mostly released at certain times of day.

It might be of some value as an adjunct to antidepressants in things like SAD (seasonal affective disorder), but I think the risk of disrupting a lot of endocrine function is a bit dodgy


----------



## Survival0200

fastandbulbous said:
			
		

> SAD (seasonal affective disorder)


Oh shite, I thought SAD meant social anxiety disorder. :D Poor me.


----------



## fastandbulbous

Well I suppose it can, just that with me, the acronym SAD instantly translates as seasonal affective disorder because I suffer from the bloody condition.


----------



## fastandbulbous

Actually as a little afternote on my ramblings about desoxypipradrol (2-(alpha,alpha-diphenylmethyl)piperidine ), I'm not sure if it has an exceedingly long half life, but otherwise it does seem to have an antidepressant effect that continues on long after the main central stimulation has ceased. I will be giving  a couple more trials at differing doses, but I don't think it's something that would appeal to your hardcore speedfreaks as it doesn't appear to produce a rush at the onset of action (that might change with higher doses or route of administration though), but more of a gradual clearing of the head. The people who would find it interesting though are those wanting something to lift their mood and allow them to concentrate for prolonged periods; also as it seems to lack the sexual arousal properties of MDPV and is almost absent of physical signs of use which makes it much more suited to essay writing, driving etc than MDPV & especially any of the amphetamines. The mood lift is quite pronounced and has a euphoric component to it, but not distractingly so as can occur with amphetamines.

The closely related compound pipradrol used to be prescribed to people on opiate dependance in the 70s & 80s to increase motivation etc and this seems to be like a pipradrol with nitrous injection. Sadly pipradrol was added to the Misuse of Drugs Act in 1977 in the UK and after that it's use/prescription slowly diminished to nothing - this compound seems like a worthy, souped up version of it


----------



## kidamnesiac

fastandbulbous said:
			
		

> Well I suppose it can, just that with me, the acronym SAD instantly translates as seasonal affective disorder because I suffer from the bloody condition.



Me too, for my entire undergrad, then I moved to sunny California %) 
and now for something completely relevant...


----------



## fastandbulbous

^ Just to end the OT bit, where were you living before going to California? I live in the N of England where even in the summer you get plenty of days where it's overcast and all that gets through is a dull grey light  

I'd probably go hyperactive & explode if I moved to somewhere that had proper summers!


----------



## kidamnesiac

The Pacific Northwest of USA. It is ALWAYS grey in the winter. It rains probably 5/7 days and is of a similar latitude to N England, so it's always twilight in the winter anyway. (and to you Seattle folk, Olympia gets twice as much rain as you!)
The summers were awesome though, 75+ days of gorgeous sunshine, which put me into long term manic-depressive. I damned near did explode when that big bright thing would break the grey shield.  
Slightly on topic, is it any wonder stimulant ABUSE is high in these areas?


----------



## Refluxer

It now looks like the tablets sold as 2-benzylpiperidine actually contained BZP. I'm not surprised.


----------



## izo

but isnt bzp sheduled in the country from where they are sold?

any theories on the effects when replacing the fluoro in 4-fluoro-amphetamine with a trifluoromethyl group? the only stimulant i know which contains a CF3 group is fenfluoramine (aka 3-trifluoromethyl,n-ethylamphetamine).


----------



## Refluxer

Yes, it's scheduled. But that hasn't stopped the vendor before.


----------



## fastandbulbous

'Benzylpiperidine' witthout the qualifying '2-' before it is almost gauranteed to be BZP rather than 2-benzylpiperidine for the simple fact that it's piss simple to synth BZP wheras 2-benzylpiperidine is a little more complex & involved. Besides the reported 200mg/dose just seems way too high for what you'd expect from SAR studies (should be somewhere in the 5-50mg range unless something really weird is happening like MAO inhibition). The corresponding compound where one of the benzyl carbon hydrogen atoms is replaced by a phenyl group is active in the 2-5 mg range and methylphenidate & levacetoperane (methylphenidate reversed ester) are both active 10-20mg.

Odd on bet the name benzylpiperidine was intended to introduce ambiguity so that people might think they are getting something 'new & improved' and not a crappy drug already known about


----------



## nuke

I don't know about the meta or para trifluoromethyl or even meta or para methyl catcholamine derived stimulants (eg nor-fenfluoramine).  They have a history of binding serotonergically in the heart valves and causing cardiotoxicity.


----------



## vecktor

Refluxer said:
			
		

> It now looks like the tablets sold as 2-benzylpiperidine actually contained BZP. I'm not surprised.



I thought as much, the clue was the dihydrochloride.


----------



## fastandbulbous

^ Didn't read that - now that you've said that though, it's patently obvious. 2-benzylpiperidine only has 1 nitrogen atom that can be protonated whereas 1-benzylpiperazine (BZP) has two ans as such forms dihydrochkirides


----------



## haribo1

F&B: I see the medical dosage of pipradrol is 2mg, what dose-range are you trying? I noticed another relative, diphenyl-2-piperadylcarbinol. Any details on that one? Would the freebase of your desoxypipradrol be smokable? I know methamphetamine salts are smoked but I've not heard of amphetamine being smoked. Your product had a secondary amine so I would think it smokable? Changing one of those benzene rings to a cyclohexane ring would be interesting as would making the piperidine to a pyrrolidine. Lots of room for fun there.
 Pity it has such a long action. One would think it pretty cheap to make. Is it like U4euh? at 50mg smoked, I found it an EXCELLENT drug for work. It's also really popular in Isreal of all places. I'm now seriously studying p-F aminorex. Finding the precursor is a bit of a bitch, but it would be legal and from what I've heard about plain aminorex, it's an excellent high at 40mg (it's more speedy than U4euh & 4 x  stronger). Any comments on that one?
 Lastly, I'm now fixated on fencamfamine. I would be fascinated to see what the methyl analog would be like. Likely to be more speedy BUT since it's mode of action is different to plain speed, you might well lose the 'magic'...


----------



## fastandbulbous

> I noticed another relative, diphenyl-2-piperadylcarbinol.



That is pipradrol - did you mean the pyrrolidine derivative?

As for the desoxypipradrol, it's a weird one in the sense yjat there's no decernable physical aspect with which to judge your level of intoxication - it is all 'in your head'. From one perspective, that's ideal as it's the physical impact on the body that makes most stimulants less than ideal, but it also means that you're inclined to up the dose of desoxypipradro; until you get a physical marker to judge things with, as I found out at a friends birthday party on Sat; got really out of it and ended up consuming nearly 30mg in one night. A couple of friends who had 10mg didn't sleep 'till last night - funnily I slept OK, but I don't seem to have a 'normal' reaction to stimulants, possibly something to do with having manic-depression (not bad, just hypomanic when on an upswing, but it means that I go through moments worse than any stimulant comedown without a drug being anywhere near my body. In comparison, stimulant comedowns have never bothered me much at all).

It probably would ber smokable as the freebase, but for me, smoking is a route of last resort so I've never had any inclination to find out. I have tried IM route with 10mg and due to the lack of the physical aspect, there's no rush as such, just a rapid sense of clarity (thinking back to my first encounter with it, maybe a touch of megalomania considering I described my state as ready to march imto Poland!). I think replacing a phenyl group with a cyclohexyl would be a step in the wrong direction (just a hunch), but it might be OK with a 2-thienyl group as a replacement.

The pyrrolidine version of pipradrol diphenyl(2-pyrrolidyl)methanol is used as an optical resolving agent and is a reasonable CNS stimulant (best to use the R isomer as it's the most active) and works well at about 20mg which is a huge drop in potency compared with pipradrol (but it's still reasonably potent, so it's worth trying!). The best thing about desoxypipradrol is the total lack of anorectic activity. Quite literally you can have your cake & eat it! 

A friend who produced some p-fluoro 4-MAR said that although the first time was excellent and that it had some entactogenic activity, subsequent usage became more & more troublesome so that eventually he just stopped using it altogether- that doesn't sound good to me at all.

Fencamfamine acts by causing efflux as well as inhibiting reuptake, so essentially it does have the same mechanism as amphetamine. Taking that into account and comparing the effects of N-ethylamphetamine with methamphetamine, I'd guess that the N-methyl derivative would be a more active stimulant, but that you;d have a lot more physical/peripheral CNS mediated effects as N-ethylamphetamine is a joy - it's not as potent as meth (~ on a par with amphetamine dose wise), but has less tachycardia etc than either amphet or it's big brother (personally I'd rate it the best of the simple amphetamine derivatives, but maybe that's just me!)


----------



## haribo1

Thats the analog I'm thinking of.

Shame that p-F AR doesn't sound like a winner. Both aminorex & U4euh are excellent. aminorex is better than speed & u4euh sounds a lot like desoxypipradrol to me. I felt very little stimulation, just clarity.


----------



## fastandbulbous

Ah, right. I've got some info on it (somewhere on a hard drive - but protected by the grat god fuckknows - as in fuckknows where it is ), but from memory it's a fairly potent stimulant of the same type I believe


----------



## Survival0200

How much of fencamfamine would be a reasonable "recreational" dose? And how much fencamfamine can you take in the form of Reactivan(R), without taking too much of those vitamins?


----------



## vecktor

Survival0200 said:
			
		

> How much of fencamfamine would be a reasonable "recreational" dose? And how much fencamfamine can you take in the form of Reactivan(R), without taking too much of those vitamins?



eating 60 mg of the hydrochloride seemed about right. lower doses don't seem to be worth it. depends on individual chemistry.
as for how much Reactivan before ODing on vitamins, I have no idea. I wasn't aware that Reactivan was available any more in Europe or US. last time I looked it was still available OTC in South Africa


----------



## fastandbulbous

I found that 30-40mg was enough fencamfamine for me to be 'as happy as a pig in shit', but due to its very low body load impact, the dose vector suggested shouldn't pose any sort of problem (unless you're a bit loose in the head and don't get on well with other stimulants). Via the IM route, 25mg produced galloping megalomania (of the fun type) where no-one can get a word in edgeways for a good 2-3 hours. 

I don't know about the safety limit with Reactivan as the fencamfamine I used was from a chemical supplier (many many years ago, before it was reintroduced to the MoDA in the mid 80's), but the most toxic vitamins are the fat soluble ones (A, D & to a certain extent E) and I think Reactivan only containd B vit complex (but you still have to use some common sense with them).

Another product that used to be next to Reactivan (ie mixed with a shitload of vitamins) was prolintane, but I can't remember the product name. Prolintane is an unusual stimulant in that it's reckoned to actually increase appetite! In appearance, it's a bit similar to MDPV, only there's no methylenedioxy ring and the beta keto is reduced to 2 hydrogen (similar to the difference between methcathinone & methamphetamine). It was indicated for the same conditions that Reactivan was - is this product (prolintane & vitamins) still available anywhere in the world these days?


----------



## jah

Basically, the only difference between desoxypipradrol and 1-phenyl-2-(n-methylamino)-1-butanone is the adrenergic activity?and duration?

Which do you like best!!8)


----------



## fastandbulbous

^ No, there's a world of difference, both in chemical structure and subjective effects; 1-phenyl-2-(N-methylamino)-1-butanone has noticable physical effects (body load ), which make it much easier to guage an ideal dose for yourself. Also it has a much shorter duration of action compared to desoxypipradrol. It might even have a slightly different mechanism of action (it could cause efflux as well as being a reuptake inhibitor) - I don't know a great deal about the minutae of its pharmacology. 

On the other hand, I still don't have a good measure of desoxypipradrol due to its almost complete absence of physical effects (body load) & that's after quite a few doses of varying sizes (2mg - 25mg). All I can be definite about so far is that it is a very effective stimulant that produces a state of clarity that you simply don't get from any of the amphetamines,  and has a bloody long duration of action. Even a 20mg IM dose didn't produce what I'd call any sort of noticable rush (again people look for a physical conformation of a rush occuring), but it did cause me to go from half asleep to fully awake with good clarity of thought within 2 minutes. Once the clarity stage is achieved, then you get a continuous climb in mood to a point of exquisite euphoria about 20 mins after the IM administration. This lasts a long time (15+ hours for 20mg IM) before tailing off gradually with seemingly little crash other than that caused by lack of sleep (IMed at 10:30am and still didn't sleep that night).

On top of that, the phenylbutanone has a fair amount of anorectic activity which I personally would rather be a lot less (I like eating far too much!); desoxypipradrol OTOH has effectively zero anorectic activity, so you could use it as a pick me up before going to a restaurant without buggering up the meal (although signs of anorectic activity were begining to show with the 20mg IM dose, but with hindsight, that's a bit excessive dosing regeime!).

If you're asking if I had a choice between 1g of desoxypipradrol & 1g (or even 10g) of 1-phenyl-2-(N-methylamino)-1-butanone, I can say that it'd be the desoxypipradrol every time, but I think your average speed freak would choose the other way as the former has no real descernable rush (well not so far into my experiments with it) whereas the latter will definitely produce the rush they are looking for.

Unlike fans of meth, I like stimulants for the ability to function with a clear head for prolonged periods and the long term mood lift whereas for meth freaks it seems to be all about the rush on initial administration (and thank god for that, as it might keep desoxypipradrol below the radar a lot longer if it's not popular with people who verge on self-destructive stimulanrt use)


----------



## haribo1

^^^A fate that lasted U4euh for about 28 years.


----------



## fastandbulbous

^ Does 4-MAR not produce any sort of rush either? I was under the impression that it did of sorts (I will get to try the bloody stuff eventually - all these false starts,  etc is just making me more & more curious!)


----------



## Survival0200

fastandbulbous said:
			
		

> Another product that used to be next to Reactivan (ie mixed with a shitload of vitamins) was prolintane, but I can't remember the product name.


The product name was Catovit® and it was manufactured by Boehringer Ingelheim. Where I live (Finland), the tablet form of it was discontinued in 1991. It was also available as a mixture, until 1982. The both forms were approved for sale in 1967, here.

Catovit® tablets had 10 mg prolintane each and the Catovit® mixture had 0,75 mg prolintane / mL.

According to my books, prolintane doesn't have any addiction potential.


----------



## fastandbulbous

> According to my books, prolintane doesn't have any addiction potential



I've seen that said about so many drugs in medicinal use that turned out to be just the opposite. Drug company PR so that their product will be widely prescribed. How long did DmithKline Beecham say Paroxitine isn't habit forming?


----------



## haribo1

fastandbulbous said:
			
		

> ^ Does 4-MAR not produce any sort of rush either? I was under the impression that it did of sorts (I will get to try the bloody stuff eventually - all these false starts,  etc is just making me more & more curious!)



50mg smoked gave a very mild lift but nothing like amphetamines. I just felt happy, awake & focussed.


----------



## haribo1

fastandbulbous said:
			
		

> If it wasn't why did the UK government feel the need to include it in the Misuse of Drugs Act...



Who can make sense of MoDA? Quite a few non-addictive compounds are listed (well, I guess you can get addicted to anything, I mean physical addiction). Things like LSD & DMT stop working if you overuse them.


----------



## fastandbulbous

^ Er paroxetine isn't in the MoDA, it seems that my brain is having a few backfires today - mind you, they originally said benzos were non-addictive, but look at all the shite associated with their prologed use nowadays


----------



## haribo1

Tell me about it. I'm on 12mg clonazepam per day. I don't feel anything. However, if I DON'T take it...


----------



## fastandbulbous

Fuck, and you were wondering how I coped with phantom limb pain. With all the greif you've been saddled with, what I get in terms of pain & distress would probably be a not too bad day for you.

There are times when we (by that I'm pointing at myself) don't appreciate how good things are in comparison to how bad they could be. I could be an amputee in a refugee camp in the Sudan if fate had decided otherwise.

Considering all the crap I've got myself worked up over in the last few days, I think I need to take a quiet moment and realize it doesn't matter, being alive and in a country like Britain is a pretty priviledged thing to have...


----------



## Survival0200

^^
Are you missing a limb?


----------



## Helios.

fastandbulbous,

Have you considered writing a blog in the Journal forum?


----------



## Refluxer

I need a little help from the Tribe of Bluelight:

Is the anyone that has *tried* _2-benzylpiperidine_ and can tell me a little about the actual effects in human?

If anyone of you SAR-geeks out there can dish me some predictions on how it may differ from methylphenidate, it  would be much appreciated.


----------



## haribo1

F&B That pipradrol analogue I posted an image of is active in sub-milligram doses apparently. Worth a look? If only desoxy was a bit shorter acting...


----------



## fastandbulbous

^ Like 1 or 2 days shorter! 20mg on a Friday night could see you awake for the whole weekend!


----------



## Refluxer

C'mon ppl! I know a few of you have the knowledge to do some qualified SAR-guessing.


----------



## vecktor

Refluxer said:
			
		

> C'mon ppl! I know a few of you have the knowledge to do some qualified SAR-guessing.


I don't like guessing but here goes:
I predict full activity at around 25-30mg. I will also hazard a guess that it is a DAT inhibitor without producing much in the way of euphoria unless smoked or snorted. I will also predict that it is shorter acting than desoxypipradol because it can be metabolised (oxidised) at the benzylic position.


----------



## Refluxer

Thank you Vecktor! 

If compared to methylphenidate, it seems likely to last a lot longer, but is the ester group involved (or restricting?) in any actual binding? Does the lack of the ester group open up for binding to other receptors than the usual stimulant ones?


----------



## haribo1

Smoking desoxy gives a 30 minute rush, mental not physical.


----------



## fastandbulbous

> I don't like guessing but here goes:



That's all I do most of the time!

Yep somewhere between 20-50mg range, longer lasting tha methylphenidate or its reverse ester as it doesn't have a handy metabolic handle. Probably excreted mostly unchanged (not many PEAs & derivatives metabolized on an unsubstiututed benzylic carbon) . Not mich at all in the way of physical effects. Basically like a little brother of desoxypipradrol.

I honestly think that 2-benzoylpiperidine would be a better bet (sort of beta keto 2-benzylpiperidine) as it'd be shorter lasting , but would show more physical effects than 2-nenzylpiperidine.

After all that, the morpholine derivative (3-benzylmorpholine) is the most potent of the series as it is with the diphenyl compounds, and it's not too difficult to synth using phenylalanine or phenylalaninol as a starting material (allows for synth of optically pure compounds very easily)


----------



## Reminisant B

*Cyclopentamine*

I was just browsing wikipedia - stimulants and saw Cyclopentamine , looks like a horrible propylhexedrine type drug. Anyone know anything about it first hand?


----------



## fastandbulbous

> Cyclopentamine , looks like a horrible propylhexedrine type drug.



That sums it up perfectly. At first glance I thought you meant 2-phenylcyclopentylamine which is a useful, pleasant locomotor stimulant with antidepressant properties


----------



## Reminisant B

Just worked out the structure of 2-phenylcyclopentylamine, looks cool! (for want of a better expression). 

Have you had experience with this compound then?

What about sticking a methylenedioxy on it ? Or would this not work for good reason, my chemistry fails me at this point or more likely pharmacology.


----------



## Jamshyd

That looks suspiciously close to Aminorex, does it not?


----------



## fastandbulbous

No (not yet )

The aryl-alicyclic amines have loads of potential, especially the ones made more rigid by a second ring (fencamfamine is just 2-phenylcyclohexylamine with a methylene bridge across the centre (or 2-phenylcyclopentylamine with a 3,5 ethylene bridge) and an N-ethyl group


----------



## Reminisant B

*Dreaming...*

Ok I'm the first to admit I am not the best at this but just thinking aloud I was looking at the structure and comparing it to desoxypipradol...

What do you think of these compounds...

Compound A is similar to 2-aminoindan and the second has an indole. Good possibility / Bad possibility?

I definately like the look of compound A (if its chemically possible)


----------



## Reminisant B

Oh and also just made the link 2-phenylcyclopentylamine is very similar to tranylcypromine Parnate® (the maoi antidepressant currently available on RX)


----------



## fastandbulbous

Compound B is an aromatic amine (which I have a great deal of mistrust about) so I'd not even consider eating any.


----------



## Reminisant B

I have just read up on some basic aromatic amines, aniline etc and the word poison came up, I think I understand.


----------



## kidamnesiac

The lipophilicity, combined with having a basically unmetabolizable group (good luck at puckering that ring correctly Mr. MAO) at the major metabolic site would make it seem that the cyclopentyl compound would last for days and days. Maybe for long range fighter pilots?


----------



## fastandbulbous

Drugs don't need to be metabolized to be got rid of (esp if it already has a polar group to facilitare the kidney's job of removing it) so it;ll just get pissed out unchanged. If you think of muscimol, it;s excreted unchanged but doesn't last for days.

Besides, from what I've read about it, it's about the same half life as amphetamine


----------



## kidamnesiac

I know about unmetabolized excretion and I know the pH dependence of the excretion for the amphetamines, it just appeared that being so fatty, this bugger would want to spend a lot of time out of the blood stream. 
but if the half-life~~amphetamine, interesting.


----------



## fastandbulbous

It's been considered as an antidepressant/psychostimulant in the past, but I don't know why it didn't make it to clinical trials. As regards the half life being about that of amphetamine, that's in several species including primates, but I can't find anything in my notes about it that refer to half life in man. Mind you, if you're getting those sort of figures for a whole range of species, including rhesus monkeys, I can't imagine that in man it;'ll be radically different.  (Sorry but refs in my notes only refer to Journal of Pharmacology & Experimental Theraputics - JPET. I didn't note down the journal no or page - I know that's my main fault, that I'm a sloppy records keeper).

As regards it's lipophillic tendancies, 2-phenylcyclopentylamine isn't going to be that different from fencamfamine w.r.t. the non-polar part of th molecule (I realize fencamfamine is a secondary amine, but it's metabolite with the N-ethyl group removed is active but doesn't hang around in the body significantly longer than its parent compound). My only area of 'what if' left surrounding it is it's ability to act as a competitive inhibitor of MAO 2-phenylcyclopropylamine )tranylcypromine/Parnate) is about the most troublesome clinical MAOI whereas fencamfamine is a competetive inhibitor that is weaker than amphetamine. Where the 5 membered ring lies on this scale is the last barrier to it being a potential 'new wonder stimulant'. Will report back when I find out one way or the other


----------



## fastandbulbous

> I definately like the look of compound A (if its chemically possible)




Compound A for some reason reminded me of nomifensine even though nomifensine is a tetrahydroisoquinoline based compound (it's like the tetralin/indan version of nomifensine!) I think it'll work, but no ideas as to potency


----------



## Reminisant B

^ I love these threads, you learn so many new compounds. 

Nomifensine does look similar, I was unaware so many Dopamine reuptake inhibitors have been available for medical use in the past. 

Until recently I was one who viewed the history of antidepressant / stimulants as being something like Tricyclics -> SSRI -> SSRI/SNRI etc & latest atypical. With Methamphetamine / amphetamine / phenmetrazine floating around in the background.

I might see if I can find any other similar compounds in the literature, Pleased my compound has passed phase one of bluelight hypothesizing


----------



## Reminisant B

Anyone heard of Sydnocarb?

http://jpet.aspetjournals.org/cgi/content/full/288/3/1298

Looks like an incredibly complicated pro-drug of amphetamine.


----------



## Reminisant B

http://www.google.com/patents?vid=U...ct&zoom=4&dq=stimulant+novel+compound#PPP2,M1

Abstract
A series of novel 4-phenyl-1,2,3,4-tetrahydro-1-naphthylamines, including their pharmaceutically acceptable acid addition salts and their cis- and trans-isomers, have been prepared. The trans-isomers are useful in the field of mental health as antidepressant agents and/or as psychomotor stimulants. The trans-isomer of N-methyl-4-phenyl-1,2,3,4-tetrahydro-1-naphthylamine represents a preferred embodiment.


----------



## fastandbulbous

Reminisant B said:
			
		

> Anyone heard of Sydnocarb?
> 
> http://jpet.aspetjournals.org/cgi/content/full/288/3/1298
> 
> Looks like an incredibly complicated pro-drug of amphetamine.



No it looks well dodgy as its not a derivative of alphamethylphenethylamine, but a dreivative of alpha-methylphenethylhydrazine (has a N-N bond) and alpha-methylphenethylhydrazine is a fuck-off non-competitive inhibitor of MAO. If iy is a pro-drug, it will form the hydrazine not the amine compound (and that isn;t at all good or healty)


chemical structure of syndocarb


----------



## vecktor

fastandbulbous said:
			
		

> No it looks well dodgy as its not a derivative of alphamethylphenethylamine, but a dreivative of alpha-methylphenethylhydrazine (has a N-N bond) and alpha-methylphenethylhydrazine is a fuck-off non-competitive inhibitor of MAO. If iy is a pro-drug, it will form the hydrazine not the amine compound (and that isn;t at all good or healty)
> 
> 
> chemical structure of syndocarb



sidnocarb has been very very widely used in the former soviet union, it is considerably less toxic then amphetamine, though is a less powerful stimulant. it has not,I believe, significant MAOI activity.
it is a member of the syndone or sydnone (the two names are interchanged though sydnone is the iupac approved name)class of drugs about which I know very little as the literature is almost entirely in Russian.


----------



## fastandbulbous

^^ Just the first thing I saw was the N-N bond and all of the phenethylhydrazines are non-competetive MAOI. I suppose if the ring isn't opened up it doesn't need to act as a MAOI. I'd need to see clinical data in English (or some language I can bribe my wife to translate from, such as Hebrew) before I'd consider eating any


----------



## Reminisant B

Sidnocarb/sindocarb/sydnocarb - I thought I had heard it somewhere before, its talked about in the carphedon thread.

Possibly might not be controlled in some countries then.....? Although by the sounds of things its not very good.

Interesting about the chemical structure.


----------



## hussness

What's the +- on the ring with the N-N-O structure on sidnocarb?


----------



## Reminisant B

^ I think* that means it can form the cation or anion form. I.e 

Sindocarb Hydrochloride

or 

Sindocarb Sodium


----------



## electromagnetic

I've been looking on Spanish language sites for prolintane (Reactivan) but they all seem to indicate it's off the market.  

This is your free 1st almost warning. Do not ask for sources again or it's warning time


----------



## vecktor

hussness said:
			
		

> What's the +- on the ring with the N-N-O structure on sidnocarb?



it means that the structure cannot be accurately represented with a simple drawing, the ring contains unbalanced charges which move around, the plus minus is just a way of trying to show this, there are quite a few nitrogen compounds which cannot be accurately represented on paper.

sidnocarb = Mesocarb

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7312716&dopt=Abstract


----------



## fastandbulbous

It sounds a lot like MDPV ie almost entiely dopamine reuptake inhibition with a tiny bit of noradrenaline reuptake & bog all effect on the 5HT system


----------



## Reminisant B

Its a bit of a strange molecule, can't really compare it to anything (now realising its not a pro-drug). Such a long, thin shape.


----------



## Jamshyd

RemB: you might be interested in reading this thread: http://www.bluelight.ru/vb/showthread.php?t=251309

Also, try the alternative spelling "Sydnocarb"... it yeilds more results on it on google.


----------



## vecktor

Reminisant B said:
			
		

> Its a bit of a strange molecule, can't really compare it to anything (now realising its not a pro-drug). Such a long, thin shape.



what chem draw program drew that? is it 3 dimensionally correct? lowest energy or whatever, I am looking for an easy to use free piece of software to do this.

mesocarb/ sidnocarb/ syndnocarb /sydnocarb


----------



## Reminisant B

I'm using ChemOffice2002 which has Chem Draw and Chem3d.

 I didn't run any of the tools to optimize it shape so it won't be the best estimate. 

I remeber reading a discussion in a blueligt thread about drawing software software, maybe in the MDPV thread, or possibly this one (its getting so big, hard to search through it).


----------



## izo

it was in the mdpv thread:
http://www.chemaxon.com/marvin/sketch/demo.html
a better version can be found here:
http://pharmazie-bonn.de/marvin/sketch-applet2.html

is fencamfamine still available for prescribtion anywhere?


----------



## haribo1

Maybe it's the brain going, but I'm sure that East European runners and such were using mesocarb until it was banned by the Olympic comittee. In fact, I seem to remember reading that there was talk of it being developed by one of the labs that generally worked on stuff to enhance their peoples performance.
As soon as I came across it, I was really interested.


----------



## mad_scientist

izo said:
			
		

> is fencamfamine still available for prescribtion anywhere?



South Africa apparantly, probably other places also.


----------



## Jamshyd

I just got an idea. First, check out the structure of Fenethylline (Phenethyline/phenetylline/fenethyline).






Now, the idea is that this breaks down into Caffeine/Theophyline (don't care which) and Ethamphetamine in the body (or Methapmpethamine and an ethylated xanthine). If someone could explain how this breakdown happens, I would appreciate it.

Now... what about this. Since I don't have a chemdraw thingy on hand, I'd like you to visualize that same molecule, but instead of a xanthine, there is another amphetamine molecule there. What would happen in that case?


----------



## vecktor

Jamshyd said:
			
		

> I just got an idea. First, check out the structure of Fenethylline (Phenethyline/phenetylline/fenethyline).
> 
> 
> 
> 
> 
> 
> Now, the idea is that this breaks down into Caffeine/Theophyline (don't care which) and Ethamphetamine in the body (or Methapmpethamine and an ethylated xanthine). If someone could explain how this breakdown happens, I would appreciate it.
> 
> Now... what about this. Since I don't have a chemdraw thingy on hand, I'd like you to visualize that same molecule, but instead of a xanthine, there is another amphetamine molecule there. What would happen in that case?



I believe fenethylline hydrolyses to amphetamine rather than N-alkylated amphetamine.


----------



## Reminisant B

Jamshyd said:
			
		

> Now... what about this. Since I don't have a chemdraw thingy on hand, I'd like you to visualize that same molecule, but instead of a xanthine, there is another amphetamine molecule there. What would happen in that case?



You mean this?

Don't know if it exists, like the idea. Would the molecule have a tendancy not to break apart into the two molecules though due to differing chemisty. (?)


I remember reading fenethyline is surprisingly hard to synth.


----------



## Morninggloryseed

Fenethylline is metabolised by the body to form two drugs amphetamine (24.5% of oral dose) and theophylline (13.7% of oral dose), both of which are active stimulants themselves. The physiological effects of fenethylline therefore result from a combination of all three drugs.


----------



## fastandbulbous

^ There are quite a few drugs out there that are basically prodrugs for amphetamine/N alkylamphetamine. Benzphetamine is metabolized to methampetamine & amphetamine


----------



## fastandbulbous

Just in case people out there are getting too excited at the prospect of all sorts of new stimulants, here's a sobering little paper about 'when stimulants attack'


I found that little gem while looking for a paper about pipradrol analogues & derivatives


----------



## jah

Well that's a reality check for all abusers!


----------



## Jamshyd

RemB: Yes, thanks for the drawing, thats exactly what I had in mind.

Would this be broken down like Fenethyline?

And would it be considered an amp. analogue legally?

MGS and F&B: Thanks a lot for the info


----------



## johanneschimpo

^ I would assume its an analogue since when you look at it, it's still just (meth)amphetamine with a large substition [which happens to be another '(meth)amphetamine' "moiety"] in place of the methyl group alone.

I hope that makes sense and doesn't sound arrogant. Also I can't believe I used the word moiety, I hope I used it correctly.


----------



## fastandbulbous

Has anybody any data on 3-methyl-1,2,3,4-tetrahydroisoquinoline, sort of like methamphetamine bent around until the methyl group is part of the aromatic ring?

Another's I've weaseled out are 2-amino-1,2-dihydronaphthalene which is reported at 1/4 potency of dexamphetamine (so about 1/2 that of racaemic amphetamine) with the tetrahydro derivative (2-aminotetralin) being about 1/8 the potency of dexamphetamine (1/4 racaemic)


----------



## Langevin

2-amino-1,2-dihydronaphthalene?  Am I missing something?  How can there be a hydroxy and amino group at the same position on a naphthalene ring?  Ahhh...I get it, half of the naphthalene ring is partially saturated.    

Confusing nomencalture.   Anything with naphthaline in it makes me cringe, an irrational fear of naphthaline...  

Interesting that the removing the of other double bond in  2-amino tetralin leads to a decrease in potency.    I wonder what 2-amino-decahydronaphthalene would be like.  Heinous would be my guess.


----------



## nuke

It was mentioned earlier that a human assay of 2-AT had been nothing short of disastrous, so proceed cautiously through the bicyclic amphetamine analogues.


----------



## fastandbulbous

^ Where was that, I can't remember seeing anything about 2-aminotetralin


----------



## Langevin

There have been whispers of late of 4-methyl-5-(3,4 methylenedioxyphenyl)-2-amino-oxazoline.  I know the naming is wrong but I just can't be assed to figure it out.  Picture 4-methylaminorex with the methylenedioxy group on the benzene ring.  I'm assuming it'll be a stimulant.

Anyone have any info on this?

There has also been whispers of the trimethoxy analogue of this.  Stimulant, psychedelic or chemical Parkinson's?


----------



## Helios.

^One would guess it would be similar to MDMA, but one would not know without trying it.

Back on Topic:
phenyl 3-morpholinyl ether hcl.


----------



## fastandbulbous

Langevin said:
			
		

> There have been whispers of late of 4-methyl-5-(3,4 methylenedioxyphenyl)-2-amino-oxazoline.  I know the naming is wrong but I just can't be assed to figure it out.  Picture 4-methylaminorex with the methylenedioxy group on the benzene ring.  I'm assuming it'll be a stimulant.
> 
> Anyone have any info on this?
> 
> There has also been whispers of the trimethoxy analogue of this.  Stimulant, psychedelic or chemical Parkinson's?




Well para-fluoro 4-MAR was reported as being entactogenic by a friend, so that bodes well for the ring substituted methylenedioxy compound being interesting (comparing amphetamine & 4-mar). Never a guarantee though, sadly!


----------



## Helios.

An important thing to remember is that dopamine's, or "DA," structure is called 
3,4-dihydroxyphenethylamine, where "di" means 2, "hydroxy" means -OH radical, "phen" stands for a particular cyclic carbon (C) and hydrogen (H) ring having C6H6 as its empirical formula, "ethyl" stands for -CH2CH2-, and "amine" meaning -NH2 or ammonia ("smelling salt") radical.  All connected in that order.

The root "dop" [long 'o'] means "very good."
Literally, "very good smelling salt."
Hope that helps someone.


----------



## nuke

fastandbulbous said:
			
		

> ^ Where was that, I can't remember seeing anything about 2-aminotetralin





> hiyall,
> 
> saw one of you speculating about 2-amino-tetralin and feel obligated to post
> a warning story i heard from dear friend of mine:
> 
> it's absolutely vile stuff and should be avoided like the plague. yes the
> rat studies look good, but no, humans are not rats and the data can not be
> easily extrapolated.
> 
> my friends experimentation with this compound 8 years ago gave him a big life
> lesson and he's lucky to still be here. now he's not so eager to test never
> before been tried compounds. it's a fine line and i advise extreme caution
> when working something up. some of my friends mishap was inexperienced
> pilot error, after several days of ramping up slowly on seperate experiments,
> he got impatient and boosted a double dose 3 hours after taking the first dose
> (was getting slight effect from first dose and figured 3 hours was enough time
> and should have peaked), then it all hit like a frieght train. very dysphoric,
> nothing like amph, sedated, sick and wierd feeling, total agony. continued
> accent and passed out completely unconscious at 4-5 hour point and came to
> consciousness about 3-4 hours later completely surprized that he was still
> alive. he was able to call friend for help at that point and seemed like was
> leaving system slowly and was going to be OK. decided not to go to hospital to
> avoid explaining situation and potential police inquiry.
> 
> friend took him to her
> house and crashed in bed feeling sick and nauseous. some 6 hours later he
> woke up middle of the night to go pee and on way into the bathroom passed
> out completely (maybe due to low blood pressure) and did a face plant into
> shower door slicing his face and severely breaking his nose. blood everywhere,
> friend wakes up and sees him in pool of blood on the floor barely able to
> maintain consciousness. was able to get bleeding stopped and then passed
> out in bed from pain. awoke next morning in intense pain and found his nose
> was on the wrong side of his face. required surgury, long recovery, etc. truly a
> nightmare.
> 
> abandon hope all yee who enter here
> 
> sincerely,
> 
> purple heart


...


----------



## fastandbulbous

Oh, right. The rat studies did look good, but that's a bit of a human disaster as regards dosing. Suppose that''l probably mean that the 3,4-didehydro version might well be dodgy as well.

Out of curiosity, do you know the dosde that caused him to black out?


----------



## nuke

Unfortunately, no..  I'm curious as to what this actually does in the brain now, as it sounds kind of like the methoxy-methylenedioxy-tetraisoquinolines from peyote that Shulgin reported about in the 70's (they had some weird effect on dopamine/dopamine neurons that I can't recall offhand).


----------



## fastandbulbous

Yeah there are various dialkyl (dipropyl mainly), ring hydroxy 2-aminotetralins that are specific agonists for various dopamine receptor subtypes, but I thought that ring hydroxylation was needed for directly acting agonists. The methoxy/methylenedioxy isoquinolines have oxygen atoms in the similar places as the dopamine agonists mentioned, so that might be the reason for their activity


----------



## haribo1

I'm wondering about p-F aminorex. that 4-methyl just seems to weaken the whole thing. Aminorex is 20% stronger than dexadrine and I'm wondering about the substitutions. p-F is known but untested on humans. p-F 4MAR has been tested on humans. the 3,4 methylenedioxy would be fun to test...


----------



## fastandbulbous

Does anybody by any chance have a copy of the following paper I can have a peek at or have access to springerlink in order to get to have a look at it themselves?

Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol...
Ferris and Tang.  J Pharmacol Exp Ther.*1979*; 210: _422-428 _

It also contains pharmacological data about 2-benzylpiperidine, which from what I can gather from looking at papers that don't cost $10 a shot is def active as a CNS stimulant (also contains info on desoxypipradrol)


----------



## haribo1

Can't we gang together & get one member a yearly subscription. Of course, it falls on that person to keep churning out all the requests but still...


----------



## fastandbulbous

Nah, I eventuaslly got a copy due to responses by some very kind BLers (cheap bastid that I am).

Turns out 2-benzylpiperidine is as active as (+) amphetamine when it comes to noradrenergic reuptake. It just gets more & more interesting!


----------



## haribo1

And it should be as cheap as chips to make. Legal as well  Who is betting that the 3,4 methylenedioxy is a close match for MDMA???


----------



## Reminisant B

Is 2-BP controlled in any country? I assume it would be considered an analogue in some because of methylphenidate. Still looks like it should be a controlled drug, as in listed as one. 

What else did the article say? sounds like it makes for a good read this article!

EDIT: Oh woops haven't been keeping up, is mentioned in the start of this thread. Interesting.


----------



## fastandbulbous

A link to the paper here


----------



## Reminisant B

Thanks. Much appreciated - shall have a good read.


----------



## Reminisant B

Good read,  what do you think about 

2-phenyl thiomorpholine 

or possibly the phenmetrazine equiv (with extra methyl group)?

2-phenyl thiomorpoline seems to be commercially available. Also spotted it in a chem catalogue with various para substitutions F, MeO, CF3 (btw this is a proper looking chemical company as opposed to "research" chemical company, so would imagine they are sold as intermediates)


----------



## Reminisant B

Another interesting one...

2-Methyl-5-phenyl-thiazolidine

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=545825

Actually not sure, looks more toxic for some reason.

Still I think the Thiophenmetrazine looks good. (possibly)


----------



## Smyth

Very interesting F&B. The trouble is it's not possible to tell just by reading those papers what the effects are likely to be like in human subjects


----------



## Refluxer

Cheers for the link to the paper. I think that was the one I was asking about some time ago. My guinea pigs are starting to drool.


----------



## kidamnesiac

That paper is hilarious
"Dozens of rats were decapitated so that thousands can be saved in the future because it turns out you can use the whole brain..."
those rats are _heroes_ 
"...and now we're going to talk about our theories on other peoples work because our data is boring and essentially unhelpful."
What I really like is that they do their experiments at 25 instead of 37, because it is easier to model (diffusion is a normal and perhaps very INTERESTING part of living organisms you lazy pre-personal-computer-linear-line-loving-surrender-monkeys!)

There is a really interesting looking short book in the references section by Maxwell et.al
structural requirements for inhibition of noradrenaline utake by phenetylamine derivatives... in "the mechanisms of nueronal and extraneuronal transport of catecholamines"

too bad its a book


----------



## fastandbulbous

Thiophenmetrazine sounds promising as does alpha,alpha-diphenyl-alpha-(3-thiomorpholinyl)methanol - detailed in the following paper:-

The Synthesis of (A), (+) and (-) a-(3-Thiamorpholiny1)-benzhydrol, a New Selective Stimulant of the Central Nervous System. B. BELLEAU Journal of Medicinal and Pharmaceutical Chemistry (1960)VOL. 2, No. 5 p553.

The paper outlines the additional benefits of using thiomorpholine because of possible metabolic activity about the sulphur atom.




> Very interesting F&B. The trouble is it's not possible to tell just by reading those papers what the effects are likely to be like in human subjects



True, but the same could be said of drugs such as 4-MAR and MDPV before they became widely used compounds (& why you dig out as much toxicology relating to primates as possible)


----------



## Aidan of TCC

fastandbulbous said:
			
		

> A link to the paper here



What, I don't get credit for finding it?


----------



## Reminisant B

fastandbulbous said:
			
		

> Thiophenmetrazine sounds promising as does alpha,alpha-diphenyl-alpha-(3-thiomorpholinyl)methanol - detailed in the following paper:-
> 
> The Synthesis of (A), (+) and (-) a-(3-Thiamorpholiny1)-benzhydrol, a New Selective Stimulant of the Central Nervous System. B. BELLEAU Journal of Medicinal and Pharmaceutical Chemistry (1960)VOL. 2, No. 5 p553.
> 
> The paper outlines the additional benefits of using thiomorpholine because of possible metabolic activity about the sulphur atom.



Wow those are some interesting compounds... I would imagine they are quite hard to synth.  

Thio compounds looks very promising in terms of new territory

What about the Benzothiophane analogue of MDMA (like benzofuran but with S instead of O) ? From trying to remember from PIHKAL isn't the MDMA thio analogue not possible or extremely hard. But the benzothiophane compound looks like its available.


----------



## haribo1

I still say go with what we know. The compound on the right is described as being 'active at sub-milligram levels' which seems like it might be good. Possibly the thioalcohol version would elicit some joy, who knows? Has any work on thioephedrine been carried out?


----------



## Jamshyd

Is it just me, or do these compounds (especially Sch-5472) bear similarity to Lefetamine?


----------



## haribo1

J- now your just getting obsessed with SPA, man! If the N in pipradrol was 1 carbon further round the ring & methylated, then it would follow the morphine rule, so that's a possible. Remember,

1-Aromatic system
2-Quaternary carbon
3-2 carbon chain
4-tertiary amine


----------



## Reminisant B

Does anyone know if other analogues of modafinil have been made and tested? (other than adrafinil + the pure isomer armodafinil) 

I understand many new pharmaceuticals may target the same receptors but I don't mean the question in that sense. 

I mean actual analogues of modafinil - like it could get interesting if something is substituted on the Nitrogen atom.


----------



## Reminisant B

Hmm shame this compound has no literature but looks interesting, almost like a modafinil antagonist.

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11960525


----------



## Reminisant B

*Benzylpiperazine-Modafinil*

What about the possibility of Connecting benzylpiperazine to modafinil. (Possible having those two as metabolites but also having new interesting effects)


----------



## fastandbulbous

^ Doesn't always work like that. You'd think that putting an alphamethylphenethyl group on a tryptamine nucleus (nitrogen of side chain)would give a speedy hallucinogen, but you get an inactive compound. The important thing is finding the receptor for a drug, then characterising it and determining the pharmacophore (ideal spacing of main functional groups)


----------



## mad_scientist

Read this paper re modafinil, very interesting...

Jia Zhou, Rong He, Kenneth M. Johnson,
Yanping Ye, and Alan P. Kozikowski

Piperidine-Based Nocaine/Modafinil
Hybrid Ligands as Highly Potent
Monoamine Transporter Inhibitors:
Efficient Drug Discovery by Rational
Lead Hybridization

Journal of Medicinal Chemistry 47(24): 5821-5824

Look at compound "16e" particularly, nanomolar inhibition of dopamine, serotonin and noradrenaline reuptake in a single molecule.

Probably best not posting the full paper on here cos of copyright infringement, site rules ban on posting synthetic routes etc, but heres the structure of 16e, synthesis is 7 steps from arecoline...


----------



## Reminisant B

^ditto, looks really interesting, any chane you could pm it?


----------



## Smyth

It's really the sort of thing that is going to stay confined to the research laboratory. Still, I could say the same about Paxil (which was/is also made from arecoline), and this has been successfully commercialized. Add to this that there are now totally synthetic routes to Paxil which apparently cut down on the cost of manufacture, and its not impossible that financial gains could be made on these novel hybrid compounds provided that they are powered by the major drug companies. 

Although not advanced discussion as such, I read and have heard from people who have tried modafinil, that it is really a bit like executive caffeine in terms of its effects. I would find it useful if people can fill me in on this compound as it is still somewhat obscure and it seems like it is gaining in popularity.


----------



## mad_scientist

I've tried adrafinil a bunch of times, back when it was unrestricted (its prescription medicine now because of its supposed abuse potential 8)  )

Adrafinil is a prodrug of modafinil so basically very similar effects id imagine, its a useful stimulant for work or study but not euphoric or abusable in any way. 

I found it good for drinking alcohol socially as it stops you getting drunk...see personally i don't really like getting drunk but its very socially awkward to just drink orange juice or something when you have to socialise with a bunch of non-drug users who drink heavily at work functions etc, so drop 1200mg of adrafinil before you go out and you can drink for hours with everyone else but it hardly affects you...


----------



## Refluxer

Adrafinil doesn't affect me very much, it makes me a bit more alert and makes it easier to focus for a while. But it doesn't keep me awake at all, like claimed for modafinil. Also, I've developed allergic reaction to it, and get red rashes all over whenever I take it. So I stay away from it nowadays.


----------



## nuke

Smyth said:
			
		

> Although not advanced discussion as such, I read and have heard from people who have tried modafinil, that it is really a bit like executive caffeine in terms of its effects. I would find it useful if people can fill me in on this compound as it is still somewhat obscure and it seems like it is gaining in popularity.



a lot of people on the imminst.org forums use it as a nootropic, there's a ton of praise and dedicated modafinilists there.


----------



## Smyth

^Thanks for that link. Another drug that interests me is selegiline but it seems as though the drug rasagiline is even more potent. In terms of somebody who actually considers 'abusable' or 'rushy' drugs desirable and is not just looking for a 'study aid', which do u think is better out of modafinil and l-deprenyl?


----------



## Xorkoth

I'm prescribed modafinil because it was suspected that I have narcolepsy (although I'm quite sure by now that it was years of excessive lack of sleep).  It's useful occasionally, but it's not very effective for me.  Caffeine keeps me up more effectively usually.  Occasionally 200mg of it will keep me wide awake, but usually it seems to have no effect or very little effect on my ability to stay awake and/or feel awake.


----------



## vecktor

*nocaine*

it is interesting that nocaine which essentially lacks a lot of the locomotor activity of cocaine and is being investigated as a cocaine theraputic Cocadone al la methadone is the trans isomer of clarkes phenyl piperidine cocaine analogs (4-beta phenyl 3-alpha methoxycarbonyl), the cis isomer with the stereochemical configuration of the win series and cocaine is probably of more interest from a stimulant rather than anti cocaine point of view. 
the cis trans  mixture produced from arecoline via grignard at RT is also very ineffective as a locomotor stimulant in rats, suggesting that whilst the trans has reasonable DAT inhibitor activity it is not a good stimulant. the predominantly cis product produced at low temperatures is however an active stimulant and has been reported in some forensic literature.


----------



## vecktor

Reminisant B said:
			
		

> Does anyone know if other analogues of modafinil have been made and tested? (other than adrafinil + the pure isomer armodafinil)
> 
> I understand many new pharmaceuticals may target the same receptors but I don't mean the question in that sense.
> 
> I mean actual analogues of modafinil - like it could get interesting if something is substituted on the Nitrogen atom.



the synthesis of 4 4' difluoro and dichloro have been reported, they are probably more active than the parent. I have not seen any test data, but I haven't looked for it.
nobody knows how modafanil works anyway so the SAR will be complex and probably unrelated to the DAT inhibtor SAR.


----------



## Smyth

Actually I also thought the (S,S) or syn isomer of nocaine is pretty poor at behaving as a stimulant. It seems that by knocking out the tropane bridge of RTI-31 to get the corresponding piperidine compound/s you somehow whitewash the psychostimulant properties of the resultant inhibitors.

The paper dealing with the oxadiazole derivatized nocaine looks like an interesting read though.


----------



## nuke

vecktor said:
			
		

> the synthesis of 4 4' difluoro and dichloro have been reported, they are probably more active than the parent. I have not seen any test data, but I haven't looked for it.
> nobody knows how modafanil works anyway so the SAR will be complex and probably unrelated to the DAT inhibtor SAR.



Hah, funny someone made those, I suspected they'd be they'd be one of the foremost attempted substituents in the series


----------



## Helios.

Have I ever mentioned 4-isopropylmethamphetamine?
15
gotta go.


----------



## MattPsy

vecktor: Isn't Modafinil a selective H3 agonist?

I too have tried Adrafinil (prodrug to Modafinil) on a few occasions - I really like it.

I'd describe it as a a cross between caffeine and methamphetamine, but with none of the "rushing energy" wired sort of feel. You just feel very, very awake, and very healthy and alert. None of the amphetamine "COME ON YOU SLOW BASTARDS!" feeling when dealing with people, there's little impatience etc.
You can go on long walks and such and well, you just don't feel tired.
And you can go to sleep on it!

I found it combined really well with traditional stimulants, as well as psychedelics & empathogens. Also, it's nice with downers such as opiates because you feel really really relaxed and nice but not sleepy...


----------



## vecktor

MattPsy said:
			
		

> vecktor: Isn't Modafinil a selective H3 agonist?
> 
> I too have tried Adrafinil (prodrug to Modafinil) on a few occasions - I really like it.
> 
> I'd describe it as a a cross between caffeine and methamphetamine, but with none of the "rushing energy" wired sort of feel. You just feel very, very awake, and very healthy and alert. None of the amphetamine "COME ON YOU SLOW BASTARDS!" feeling when dealing with people, there's little impatience etc.
> You can go on long walks and such and well, you just don't feel tired.
> And you can go to sleep on it!
> 
> I found it combined really well with traditional stimulants, as well as psychedelics & empathogens. Also, it's nice with downers such as opiates because you feel really really relaxed and nice but not sleepy...



indeed modafinil might be a selective h3 agonist, though some assays show no interaction with the human h3 receptor see link below. I have also seen it classified as an alpha 1 agonist, somehow something to do with GABA tone, a dat inhibitor, (it is a mild dat inhibitor) something to do with orexin etc etc. If the current theory is H3 agonism then I'll go with that.
either way in my experience modafinil is a very useful and productive substance, gets rid of the accumulated sleep deprivation. 

there is a full free article on the wakefulness promoting activities of h3 antagonists here

http://www.nature.com/bjp/journal/v143/n5/full/0705964a.html
V


----------



## Helios.

modafinil is as weak as water.
yes, vecktor we know you're smart.
you have nothing to prove wrt that here.
even PhreeX will tell you modafinil sux.
if you want a less "OMW IM TOO TWEAKED" than METH drug, try 3-MEO-METH.
It's stronger than either METH or MDMA, but not exactly like either.
More spun-proof but also more durastable.
A true astrodrug.


----------



## Smyth

A ref. for that would be awesome, to prove this isnt another one of your philosophical speculations. I mean what people want is actual hard evidence (not just imaginary ideas).


----------



## yoyoman

Since modafinil is almost insoluble in water, and it doesn't look like you can make some salt sol. either, I guess that makes it mostly uninjectable (unless something like DMSO or whatever works and is safe is used to dissolve it).


----------



## fastandbulbous

DMSO leaves a horrible taste in your mouth a minute after making contact with skin - the idea of directly introducing it to your bloodstream makes me wince at the thought of that taste!


----------



## jah

I work with DMSO on a daily basis, contact with just a minute amount ,will give you a horrible taste , all day long as far as injecting it , it also  burns like hell (i wouldn't recommend it)


----------



## electromagnetic

*Rip-off*

As you're a greenlighter you get a friendly hint instead of bringing down all sorts of shit

NO SOURCES FOR *ANY* REASON


----------



## Jabberwocky

What did you expect with a name like the company you ordered from has? Generally, you want to steer clear of any business marketing tryptamines/phenethylamines as drugs. This is a pretty easy way to distinguish the scams, at least.

Usually all you get is an email txt file with what is available/prices, no fancy website or advertising.


----------



## slopoke

Anyone else think this is going into too much information 

Nothing to do with sources please, its in the BL user agreement!


----------



## dbailey11

Yeah but it's pretty common kwowlege by now that site is bogus. So, he technically he didn't give source (yes he did & he will not do it again), he just added to what many already know. It's not source if said site is a wellknown ripoff scam (yes it is according to the BLUA). Since BL is about harm reduction, that post might help some people who don't know know.
Anyway, that's just my opinion


----------



## fastandbulbous

No sources discussion for ANY reason (and I mean any reason). Further breaches will get more than a slapped wrist


----------



## dbailey11

Well I apologize then


----------



## fastandbulbous

^ no need to, you sisn't make the source post (just didn't quite get the context of 'no sources talk' and eveybody makes little mistakes - esp mods who are half asleep while checking a forum! )


----------



## bydefinition

*back on topic*

3-ethylmethamphetamine.
3-propylmethamphetamine.
3-isopropylmethamphetamine.
3-(n)-pentylmethamphetamine.
4-propylmethamphetamine.
4-(n)-pentylmethamphetamine.

Do Your Homework!!!


----------



## Vanadium

I was dreaming about cathinone and methcathinone analogs : what about putting a methylene group on beta position of amphetamine nucleus ?  The alkene is electron-rich and quite less polar than a carbonyl. 

I'd also like know if the beta-methoxyamphetamine has been tested or synthethised ; shlugin talk about b-methoxy-phenethylamines in pihkal (BOx compound) and BOD seems to be a nice psychedelic.


----------



## fastandbulbous

Beta-methoxyamphetamine is O-methylcathine (O-methylphenylpropanolamine) and beta-methoxy methamphetamine is O-methylephedrine. O-methylephedrine is like phenmetrazine with the ring cleaved between the ethylene bridge between the O and N atoms. Years ago it was on my to do list, but never got around to it. It looks very promising.

The beta-methyleneamphetamines (cathenine as Vanadium called it) is the basic structure I suggested would be possibly a more potent 5HT2a agonist when ring substituted than the corresponding amphetamines (see ;Acid, dragonflies & the 5HT2a receptor')


----------



## Reminisant B

F&B do you by chance have any literature or have an opinion on C-Indan-1-yl-methylamine? (your opinion is always apreciated btw  )

Can't find any info on it at all, wondering if it might be good. After seeing the SSRI/SNRI effects in the entactogens thread got a little too excited (slightly sad I know but there you go)


----------



## fastandbulbous

> F&B do you by chance have any literature or have an opinion on C-Indan-1-yl-methylamine?



No, sorry & yes: I haven't a clue! It looks a bit like the cyclobutane derivative of 2C-B that has cropped up occasionally


----------



## B9

^ Meh I am bereft! 

 Oh dear meaningless random posts in here !! How does one deal ?

 Stimulants of the NOW are my concern !! LOL !!!!!!!


----------



## Jamshyd

The fact that beta-keto amphetamine analogues suck (IMO) yet so many people continue to fantasize about their analogues suggests that they insidiously activate certain reward pathways, haha.


----------



## Refluxer

Did anyone do/find any more info on 2-benzylpiperidine? It seems unreal that it wasn't investigated in the era when methylphenidate was developed. I would really appreciate any info on this substance. Please send me a PM if you for any reason do not wish to discuss it in the open.

Activity is, of course, of interest - but it's almost secondary to possible toxicity that differs from methylphenidate.


----------



## MattPsy

I too would realllyyy like any info on it avaliable!


----------



## fastandbulbous

Jamshyd said:
			
		

> The fact that beta-keto amphetamine analogues suck (IMO) yet so many people continue to fantasize about their analogues suggests that they insidiously activate certain reward pathways, haha.



The thought of a drug impacting on dopaminergic reward pathways is another tin of worms alltogether (psychological dependance on the thought of drugs - quite a few of us got that real bad!)


----------



## bydefinition

*true story.*

Years ago, I went to the science library to uncover the almost 100 year old German process of methylphenidate (Ritalin) manufacture, which is far from elegant.

Later, I decided to hybridize methamphetamine with methylphenidate, losing the cocaine benzyl methyl ester.  The result, which I mentioned years ago at the hive  but never made (although I have snorted it) is called 2-BzP.

No synthesis discussion

As far as toxicity, 2-BzP is less toxic than METH (no deamination catabolic reactions; ammonia and methylamine are toxic in vivo) but more so than Ritalin (methylphenidate)--mainly b/c 2-BzP lasts longer than methylphenidate b/c methyl esters are intrinsically easy to metabolize in short order by a living animal.

Note to world:  I can't answer PMs yet.


----------



## Refluxer

Thank you very much for the information. I love empirical data! :D Skip synth details though, or you'll probably get moderator-wrath.

So how was it qualitatively, and what dosages did you try?


----------



## bydefinition

About a gram.
I had a nightmarish vision.
Other than that, it was similar to smooth but strong and long lasting meth trip.


----------



## fastandbulbous

1000mg dose? Considering the data I've accumulated so far points to a human dose being between 10-40mg, that must be getting towards a toxic dose (it's as potent an inhibitor of catecholamine reuptake as dexamphetamine)


----------



## Refluxer

^ Agreed. Who on earth, with the least knowledge of chemistry and pharmacology, would volontarily initially take one gram of a substance one is naive to? Especially considering structural likeness to methylphenidate. You're full of it until further explanation of this madness.


----------



## vecktor

bydefinition said:
			
		

> About a gram.
> I had a nightmarish vision.
> Other than that, it was similar to smooth but strong and long lasting meth trip.



I assume you have met helios? I'm sure you two would really get along well


----------



## johanneschimpo

I'm sure they're the same person 

See similarities in their schizophrenic ramblings


----------



## bydefinition

It was over a period of 3 days.
And it was crystal (or thereabouts).
And I don't know what the purity was.

Also, I would prefer it if you guys would refer to me as "chemically gifted" or "chemically psychic" or just plain "knowledgeable" rather than "schizophrenic" which I am most certainly not.  Thanks.

PLUR.


----------



## Reminisant B

Just been reading about 3-phenyl-1-indanamide compounds, although not all the pages are on the google article which is annoying. 

_3-Phenyl-1-indanamines. Potential Antidepressant Activity and Potent Inhibition
of Dopamine, Norepinephrine, and Serotonin Uptake
Klaus P. Bergeser,*t A. Vibeke Christensen,t John Hytte1,t and Tommy Liljeforss
Departments of Medicinal Chemistry and of Pharmacology and Toxicology, H. Lundbeck AIS,_

http://pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/1985/28/i12/f-pdf/f_jm00150a012.pdf?sessid=6006l3

http://www.springerlink.com/content/p80t137101273264/
_
Pharmacology in vivo of the phenylindan derivative, lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain _

*Would be interested in 3-phenyl-2-indanamide, but can't find any references.*


----------



## Reminisant B

Just realised the lu 19-005 compound is actually more similar to sertraline. 

Still there might be a 3-phenyl-1-indanamide compound which is more in tune with dopamine type stimulants.

And still I am intrigued by the 3-phenyl-*2*-indanamide idea.


----------



## Smyth

Dude, the references are from '85 and are for setraline's twin brother indatraline. 

The 3-phenyl-2-indanamide may or maynot be a good idea. Such novelties require literature based verification to prove their validity.


----------



## Reminisant B

These look an interesting set of compounds! 

Neurochemical and behavioural profile of Lu 17-133, (±)-trans-4-[3-(3,4-dichlorophenyl)-indan-1-yl]-1-piperazineethanol, an inhibitor or the uptake of dopamine and noradrenaline

http://cat.inist.fr/?aModele=afficheN&cpsidt=7292386


----------



## Reminisant B

Smyth said:
			
		

> Dude, the references are from '85 and are for setraline's twin brother indatraline.
> 
> The 3-phenyl-2-indanamide may or maynot be a good idea. Such novelties require literature based verification to prove their validity.



Right just realised its indatraline (I am still learning sorry  )

Still what do you think  about the piperazine analogue above, seen it before?


----------



## Smyth

Never seen it before. It looks OK I guess but technically WAY beyond the reach of the wishful garage chemist.


----------



## Refluxer

bydefinition said:
			
		

> It was over a period of 3 days.
> And it was crystal (or thereabouts).
> And I don't know what the purity was.



Over 3 days sounds a bit more reasonable.


----------



## haribo1

I still say that this stuff is deserves more attention (the right one). Active at sub-milligram levels, shorter T1/2 that desoxypipradrol. Wonder what esterification would do or making the reversed ester? Esterification would bring down the BP at least and might produce a 'prodrug effect'...


----------



## vecktor

Reminisant B said:
			
		

> Right just realised its indatraline (I am still learning sorry  )
> 
> Still what do you think  about the piperazine analogue above, seen it before?



this looks a lot like the gbr12909/ vanoxerine pharmacophore  minus the fluorophenylmethoxy ether with the indanyl moety locking the alkyl chain rigidly in a certain configuration.

GBR type reuptake inhibitors are a waste of time from a stimulant point of view, as they almost always inhibit dopamine release. they also appear to bind at a different location on the DAT to cocaine.

indatraline is very potent substitutes for cocaine and is extremely >20hr long lasting, but given its slow onset is unlikely to be euphoric. there is a related cyclopropane which is also very potent but I cannot remember its name.

I assume everyone interested in this, has read the Singh review chemistry design and structure activity of cocaine antagonists, deals with most of the major DAT SERT inhibitor families chem rev 2000, 100, 925-1024 is online somewhere 
v


----------



## Smyth

I have my suspicions that Sch-5472 may be an active metabolite of _desoxy_-pipradol anyway.


----------



## fastandbulbous

> I assume everyone interested in this, has read the Singh review chemistry design and structure activity of cocaine antagonists, deals with most of the major DAT SERT inhibitor families chem rev 2000, 100, 925-1024 is online somewhere



Yeah it has info regarding the pharmicophore with respect to the placing of the aromatic and amine groups and how good a fit different configurations match that with the rigid norborane like structures. The psuedotropane like configuration of amine & aromatic group seem the more potent in inhibiting reuptake as opposed to just sitting in the active site with little overall effect. The GBRs - can't remember, do they have the tropine type configuration of phenyl & amine groups?.

The piperidine analogues of cocaine don't have that ethylene bridge, so aren't rigidly in held a set distance apart due to the modified chair/boat like conformational changes that can occur. I wonder if 4-phenylqunuclidine would be a good reuptake inhibitor? I've read that 2-methyl-3-phenylquinuclidine is reasonably efficient inhibitor of DAT


----------



## fastandbulbous

Refluxer said:
			
		

> Over 3 days sounds a bit more reasonable.



Why wasn't it stated in the first place? Unless some indication of repeated dosing is given then a dose like that is taken to be a single dosage unit. A bit off from the harm reduction point of view (even 'an average of 330mg/day' would have helped)



> 2-BzP is less toxic than METH (no deamination catabolic reactions; ammonia and methylamine are toxic in vivo)



They are, but deamination in vivo leads to urea/substituted ureas and you don't get methylamine from meth (it is first demethylated to amphetamine before deamination). 2-Benzylpiperidine is most likely excreted unmetabolized for the most part. By the time it takes to ring open the piperidine or stick a benzylic OH group on, chances are it would be mostly in the bladder


----------



## Dr.Heckyll

haribo1 said:
			
		

> I still say that this stuff is deserves more attention (the right one). Active at sub-milligram levels, shorter T1/2 that desoxypipradrol. Wonder what esterification would do or making the reversed ester? Esterification would bring down the BP at least and might produce a 'prodrug effect'...



Somewhere in the article on SH-7452 they mention that the effects are unreliable:
Compound
14 had minimal cardiac arid respiratory effects at
stimulant doses and was tried ~linically.~I t was a
potent stimulant, but the dose-response effect mas too
marked. At a given dose, due to the variation in the
individual patient response, the level of stimulation
attained frequently was above or below that desired.
Journal of Medicinal Chemistry  (1968),  11  792-6

The patent on it is US 3218330.


----------



## haribo1

Dr.Heckyll said:
			
		

> Somewhere in the article on SH-7452 they mention that the effects are unreliable:
> Compound
> 14 had minimal cardiac arid respiratory effects at
> stimulant doses and was tried ~linically.~I t was a
> potent stimulant, but the dose-response effect mas too
> marked. At a given dose, due to the variation in the
> individual patient response, the level of stimulation
> attained frequently was above or below that desired.
> Journal of Medicinal Chemistry  (1968),  11  792-6
> 
> The patent on it is US 3218330.



Well thanks for that. I'm wondering if the kinetics are any better when we increase the dose from theraputic to recreational? Could you say what dose range they were testing? I tried desoxypipradrol at 30mg and I'm pretty certain thats well above any theraputic range but it was very good.
Also, like I mentioned, esterification might be an interesting move, as would the reversed ester (like ritalin and co) from a kinetics POV). Desoxy was a real winner barring it's T1/2 so fixing that would be a worthwhile project.


----------



## Smyth

haribo1 said:
			
		

> Also, like I mentioned, esterification might be an interesting move, as would the reversed ester (like ritalin and co) from a kinetics POV). Desoxy was a real winner barring it's T1/2 so fixing that would be a worthwhile project.


*War, that's creamy!  *​


----------



## haribo1

Smyth said:
			
		

> *War, that's creamy!  *​



Tilt:D


----------



## Refluxer

fastandbulbous said:
			
		

> Why wasn't it stated in the first place? Unless some indication of repeated dosing is given then a dose like that is taken to be a single dosage unit. A bit off from the harm reduction point of view (even 'an average of 330mg/day' would have helped)



Of course it's fishy, and outrageous from a harm reduction POV. BTW On a swedish forum, a guy took one gram of what was sold as R-2-benzhydrolpyrrolidine, but obviously mixed with something else. Then some MDPV to top it. And he didn't make a sound for several days - people grew a bit worried. Anyway, he recently posted again and said he was still slightly on, and IV benzos had not helped very much. Clearly, that forum is not too much of a harm reduction forum. I wonder what the crap was mixed with (and how much) - obviously it had a "taste" of menthol in the nose if you snorted it. Would you get very wired on 50-100 mgs of the supposed compound?

EDIT: The benzos helped, but because of the long duration, as soon as their effect subsided the stimulant effect shot right up again, and many redoses had to be administered. Apparantly, the experience included a 5-day visit to the hospital.


----------



## bydefinition

I don't usually do a gram of crystal at once.  

As far as Harm Reduction, this board is imo primarily a source of Harm Reduction Information.  How you choose to use that information is 100% up to you and is also imo your prerogative.

Just as some ppl may attend church or uni and apply nothing of it to their lives, other blers may od (eg PhreeX) and or die (quicksilver).  How other ppl do their drugs is of less concern to you than it is to them; in fact, it is none of your business in most cases.

Amphetamines and methamphetamines are from an LD50 standpoint, quite a bit safer than opiates and many other classes of drugs.  If someone wants to kill himself or herself (ie Kurt Cobain), you cannot stop them.  

Others do not even care.

But and to answer your question, I would if I had any 2-BzP (I accept donations btw) take between 100 and 250mg right now but YMWV usually.


----------



## Refluxer

Ymwv?


----------



## slopoke

Think he means- Your Mileage May Vary!

^ as to the muppet from another forum, i'm sure he bought from 'the leather' one and as such he deserves what he gets!!!


----------



## fastandbulbous

> As far as Harm Reduction, this board is imo primarily a source of Harm Reduction Information. How you choose to use that information is 100% up to you and is also imo your prerogative.
> 
> Just as some ppl may attend church or uni and apply nothing of it to their lives, other blers may od (eg PhreeX) and or die (quicksilver). How other ppl do their drugs is of less concern to you than it is to them; in fact, it is none of your business in most cases.



Well it is if you want to follow the harm reduction ethos. If they're using a dangerous route of administration, you hasve to know about it in order to advise them of how dangerous that route is (eg people smoking MDPV with a 2 % pyrrolidine impurity)



> I don't usually do a gram of crystal at once.



This isn't crystal, it's 2-benzylpiperidine which will have differences in dose, pharmacology, toxicology etc. Might be that it requires 250mg to get the best from it; then again 2.5mg might do the trick. Your post gave the impression that the gram was all consumed at the same time - anybody using that as a dosage guide could be in danger.


----------



## Morninggloryseed

bydefinition said:
			
		

> Also, I would prefer it if you guys would refer to me as "chemically gifted" or "chemically psychic" or just plain "knowledgeable" rather than "schizophrenic" which I am most certainly not.  Thanks.
> 
> PLUR.



Pretending that you have synthed and tried something, and wording it just so, makes you a dishonest charade of a 'person', if not an outright liar.  It certainly DOES NOT make you gifted or knowledgable, but perhaps creative.


----------



## fastandbulbous

> Pretending that you have synthed and tried something



If this is the case, it goes so completely against the harm reductionethos of BL that I'll be seeing the admin staff. At least Helios says that it's a 'psychic assay', thus indicating that it's not hard fact, but his opinion




			
				bydefinition said:
			
		

> 3-ethylmethamphetamine.
> 3-propylmethamphetamine.
> 3-isopropylmethamphetamine.
> 3-(n)-pentylmethamphetamine.
> 4-propylmethamphetamine.
> 4-(n)-pentylmethamphetamine.
> 
> Do Your Homework!!!



I have spent an hour searching for any of these compounds without success. Comments like the 'do your homework' indicate that you have a reference for them, if so please cite it as in light of MGS's statement, I want to see a ref for the above as making guesses and touting them as actual hard fact will not be tolerated. 

Doing such things is dangerous should anybody treat them as fact and if it's made up/guesses without saying so it's also somewhat sad as well


----------



## fastandbulbous

Refluxer said:
			
		

> Of course it's fishy, and outrageous from a harm reduction POV. BTW On a swedish forum, a guy took one gram of what was sold as R-2-benzhydrolpyrrolidine, but obviously mixed with something else. Then some MDPV to top it. And he didn't make a sound for several days - people grew a bit worried. Anyway, he recently posted again and said he was still slightly on, and IV benzos had not helped very much. Clearly, that forum is not too much of a harm reduction forum. I wonder what the crap was mixed with (and how much) - obviously it had a "taste" of menthol in the nose if you snorted it. Would you get very wired on 50-100 mgs of the supposed compound?
> 
> EDIT: The benzos helped, but because of the long duration, as soon as their effect subsided the stimulant effect shot right up again, and many redoses had to be administered. Apparantly, the experience included a 5-day visit to the hospital.



Actually, if it was the R isomer, he wouldn't need anything else adding to it. I found that 25mg of it (aka diphenyl-2-pyrrolidylmethanol) was enough to keep me typing most of the night. It doesn't have a large euphoria potential, but the recommended dose is 2-4mg; 250-500x that dose would cause days of CNS stimulation as you describe. From memory I think it left a strange 'menthol-like taste in my mouth even from rectal admin. What the hell was anybody doing necking a gram of this stuff - it's like desoxypipradrol & pipradrol in the aspect of physical symptoms of activity. Makes it a bit more difficult to recognize the onset of the drug, but even someone with shit for brains should be able to notice the effects of say 200mg of the (R) isomer as being too much.

Some people are their own worst enemy


----------



## Reminisant B

*1-substituted BZP's*

Ok so BZP isn't everyones favorite stimulant but what about substitution on the 1-carbon.

Having just looked at the structure of cyclizine (anti-histamine) and bzp in 3-d they appear to overlap a lot. 

Possibly a small substitution might have stimulant and anti-histamine properties. (?)


----------



## bydefinition

You are in no way obligated to believe a word I say; however, please do refrain from calling me a liar.

By typing "Do Your HW" I mean go whip up a batch and eat some.


----------



## kyanite

"You are in no way obligated to believe a word I say; however, please do refrain from calling me a liar."

Just me, or is that sentence illogical.
Either way, I'd like to think bluelight and it's members have a kind of reputation, then really what you're doing is marring it. 

Hey, remember the guy who claimed to have made pounds of some fentanyl analogue without a mask, and ended up going insane on here, talking about role playing or something.


----------



## izo

there seem to be different intentions when it comes to new stimulants. one side wants something providing a good rush and beeing strongly euphoric, kinda legal methamphetamine substitute.
others tend to find some primary safe compounds that can be integrated in their everyday lifes.
both of these profiles in one molecule would be the stimulant of the future but something tells me that this is not possible.



> I found that 25mg of it (aka diphenyl-2-pyrrolidylmethanol) was enough to keep me typing most of the night.



regarding this compound, is it true that, analogous to pipradol and desoxypipradol, it might be more potent without its hydroxy-group?


----------



## fastandbulbous

I'd say not as potent, but with stronger CNS stimulation (that's really what happens re pipradrol & desoxypipradrol). It has to do with the Ki for receptor binding vs the Ki for reuptake inhibition


----------



## MDPVagrant

Deleted ('real' deletes seem to keep resurrecting themselves, so hopefully THIS method works).


----------



## Reminisant B

*Does anyone have any information on 2-Benzhydryl-pyridine? Unsaturated desoxypipradrol*

In a paper I have on dopamine re-uptake inhibitors from the figures it appeared to bind quite well to the DA uptake site compared to other chemicals. 

Although as its very planar I assume its quite different from desoxy-pipradrol. Only really become interested in it when I realised the structure of Bisacodyl (an OTC Stimulant laxative). Had that brief thought of "wow cool you could turn an OTC laxative into a stimulant! " It probably means 2-Benzhydryl-pyridine has some horrible laxative side effects (as well as many others or reasons why it won't work)  even if it did work as a CNS stim.


----------



## Refluxer

Well, if you can make the pyridine from the laxative, then you can make the piperidine from the laxative.


----------



## dbailey11

I don't know jack about chemistry but I fuckin' love this thread!!!


----------



## General alcazar

I disagree with MDPVagrant - MDPV is really in the reacreational meth substitute camp. Too compusive to use in low doses long term. Eventually it leads to higher, compulsive dosing in most if not all that take it. Sortof like using coke to get through the day. Works for a while, but eventually will get out of hand.


----------



## phillfone

joystick said:
			
		

> I have a prescription for phenDImetrazine (phenmetrazine with an extra N-methyl group).  Phendimetrazine is metabolized by the body, according to my Physician's Desk Reference, to phenmetrazine and phenmetrazine N-oxide.  While I enjoy my monthly phendimetrazine fix, it does not compare to methamphetamine.  Neither does Ritalin (methylphenidate) or Adderall (amphetamine).
> 
> I think clear, recrystallized, nearly pure dl-methamphetamine hydrochloride is probably going to remain king of the stimulants for some time.  Its synthesis is easy, it is chemically synthesized from a naturally occurring alkaloid derived from the Chinese ma huang plant, the quality of its high is very good, and the high lasts a long time.  However, I would like to try the heretofore unscheduled 2-benzylpiperidine, a methylphenidate analogue designed to have a much longer half life than methylphenidate, as a possible stimulant.
> 
> Cocaine doesn't last long enough for me, is too expensive, and has agonizing come downs.  Plus, the first thing many people do after doing some cocaine is have to take a nasty shit while they are high.  Sure, some cocaine analogues may be very powerful, but they will always be extremely expensive to synthesize as long as they rely on cocaine as their starting material. As for the entactogens, I don't think MDMA / MDA can be beaten either, even though I am on methylone (that is, MDMCAT) right now.  OTOH, I would like to try 3,4-dichloromethamphetamine.
> 
> Caffeine and nicotine, two legal stimulants, will probably also continue to be used extensively in the future.  Speaking of nicotinic agonists, I would also like to try ABT-594.
> 
> Modafinil and ephedrine are crap drugs in my opinion.



Yes meth sooo good but is a very potent and addictive drug, its a pandoras box that must be treated with respect.   I live in country were bzp is legal, the high is good like meth but many hot cold flushes, major shrinkage, dehydration, and and the come down is a son of a bitch two days of anger.  the tetraflourophenyl piperizine is pretty good the high is nice and happy and talkative, but the comedown is even worse than bzp.  Personally i have found selegeline 
to be a very good sustainable mood booster with positive side effects such as feeling younger, protecting against cell damage.  It is amazing If i was on it i could smoke seven joints before bed, wake up at 6am and feel refereshed and ready to go 365 days of the year.


----------



## bydefinition

I am not sure either about the physical safety of 2-BzP, specifically a 2-BzP binge (for but one example the risk of dehydration and rhabdomylosis); however, I would only that I not have any now sample 
3,4-MDO-2-BzP for the experience if nothing else.

So maybe 2-BzP is probably not for the masses, but an interesting and addictive aside no less nonetheless.  Also, there aren't many numbers of people left.  

If you're going to be a hard core drug addict, it is a good idea to get stuck with something new periodically I guess--to be a neo-beatnik droga yoga etudiante universal you've got to keep going with the flow and take what good you can get while you can get it.  Also know your limits.

Nothing has been lost.
It's all there still.
There is more to be invented and explored.


----------



## bydefinition

*here comes a/the crystal*

3-(that is, meta-)-methoxyamphetamine hcl.


----------



## Mal hyde

how about  3-fluoromethylamphetamine , I'd wack that shit up not worries !


----------



## bydefinition

told you


----------



## MattPsy

Why put Ph-(CH2)-R ?
Why not just benzyl?

Your names are frequently difficult to interpret.


----------



## izo

isnt this his intention when posting?  

i remember a short table beeing posted here listing 3- and 4-fluoroamphetamine and its affinties for rat brains. did it also feature 3,4-difluoroamphetamine?


----------



## General alcazar

Well, maybe just me, but I found 4FMP to be a waste of time, money and dopamine. Mildly speedy like amphetamine and no empathogenic effects up to 150 mg. Tried it in combo with methylone and ethylone and only added to the cracked-out comedown. There must be considerable user variability in this molecule, and given the dramatic toxicity of it's close cousins, I am not to enthused by this one...


----------



## hussness

Here's one I haven't seen discussed before: (R)-5-phenyloxazolidine.  I did an ACS journal search and a pubmed search and haven't been able to find the compound mentioned.  It's almost a cross between phenmetrazine and aminorex.  Anyone familiar with this?


----------



## Reminisant B

Similar compound to that I remember seeing on pubchem...

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=637720

wasn't sure whether it would be any good as stim though. 

(R)-5-phenyloxazolidine definitely looks like it should be. 

Does anyone know what happens if you start adding groups on the benzyl parts of desoxypipradol?


----------



## jah

Does anyone know if desoxypipradrol and pipradrol would breakdown to the same metabolites?8)  

Thanks.


----------



## Refluxer

I'm guessing yes, but in different ratios from eachother. I'm very new to the metabolic pathways, and I'm not sure because of the disubstitution on the benzylic position. Perhaps desoxypipradrol is aromatically oxidized to a larger extent than pipradrol.


----------



## hussness

Here's another chemical along the lines of my last post which I'm not sure has been probed.  It's slightly more along the lines of a cyclic cathinone derivative.


----------



## fastandbulbous

^ The analagous pyran is an active stimulant and moderate appetite supressant, but that's all I can remember off the top of my head (the pyran was one of a bucketload fed to rats)


----------



## dbailey11

Alright, I got the tibby tip on the _ultimate_ stimulant of the future. Ready...

*GODSPEED*

HAHAHA, Sorry, fuck me man I couldn't help myself


----------



## johanneschimpo

Funny


----------



## fasteddie

General alcazar said:
			
		

> I disagree with MDPVagrant - MDPV is really in the reacreational meth substitute camp. Too compusive to use in low doses long term. Eventually it leads to higher, compulsive dosing in most if not all that take it. Sortof like using coke to get through the day. Works for a while, but eventually will get out of hand.




To me, the real bad downside of MA is the incredibly prolonged duration of action. There's no ester bond to hydrolyze or OH group to glycosylate. Does this compound you allude to have that quality? 

When, once upon a time, I might have ingested MA, I'd get so sick of it. Though, I was never a daily user, even at my worst.

Pardon me if this info has been discussed already. This is a very long thread.


----------



## nuke

The duration for MDPV is about 2-4 hours.  MA usually last 7-10 or so (at least, for me).


----------



## fasteddie

nuke said:
			
		

> The duration for MDPV is about 2-4 hours.  MA usually last 7-10 or so (at least, for me).




Ahh, thanks.

The search for a happy medium...MA is too long. Cocaine is too short, as well as being hideously expensive, and the fact that one is thereby subsidizing some of the worst dirtbags on gods green earth.


----------



## haribo1

fasteddie said:
			
		

> The search for a happy medium...MA is too long. Cocaine is too short, as well as being hideously expensive, and the fact that one is thereby subsidizing some of the worst dirtbags on gods green earth.



Very good point. MDPV is nice, but I would guess it has the potential to be very addictive. Wonder if anyone has tried MDPV with cocaine?


----------



## hussness

Wouldn't the much higher affinity of MDPV for DAT and NET block most of the effects of the cocaine?


----------



## MDPVagrant

Deleted


----------



## dbailey11

I'm going to apologize right now for my question- but I'm interested. If cocaine is a dopamine agonist, and l-dopa is a dopamine precurser, why are they nothing alike in terms of effect?


----------



## hussness

^The link I've pasted below should shed some light on that.

http://www.bluelight.ru/vb/showthread.php?t=301915


----------



## fasteddie

Ahhh, now I get it. methylene dioxy pyro valerone. I'm a bit slow on the uptake, today.

How about plain pyrovalerone? I see that's been scheduled a number of places, but I find little information about it otherwise. I found out about it lurking here.


----------



## dbailey11

Good lord that's alot of text to plod through. Anyone with a slightly condensed version care to answer? Thanks none the less hussness.


----------



## haribo1

MDPVagrant said:
			
		

> It might block some of cocaine's dopaminergic effects, but IMO MDPV is actually a good deal better than cocaine in this dept. so it would hardly matter.



That's why I thought it might be good with cocaine or some related compound...


----------



## Reminisant B

MDPVagrant said:
			
		

> Of course, it lacks cocaine's vasoconstricting and (some of) its cardiotoxic effects, so it's a tradeoff I guess...  I'd take MDPV over coke any day as far as sex boosters/aphrodisiacs go, but coke definitely wins the day in a social/party atmosphere.



Possibly in terms of harm minimisation its not ideal to make statements suggestive off MDPV being less toxic than cocaine. 

Even drugs that have passed phase III clinical trials can be withdrawn. 8( Can sometimes be better the devil you know - cocaine is far from ideal (toxicity) but A LOT is known about it.


----------



## MDPVagrant

Reminisant B said:
			
		

> Possibly in terms of harm minimisation its not ideal to make statements suggestive off MDPV being less toxic than cocaine.


Good point... consider this a retraction of any such statement I may have made (deleted earlier posts anyway).


----------



## Jamshyd

MDPVagrant said:
			
		

> Uhhmm... a lot is known about PURE cocaine, yes.  Do you know anybody who's ever received it in that state?  I don't.


Yes - pharmaceutical cocaine used to be freely available in the late 19th and early 20th century. There are some subjective writings about its recreational use in that form, and it appears to be rather safe compared to other stimulants.

Coca leaf has been used for centuries, and in that form, it is absolutely non-toxic (as a matter of fact, it is actually _healthy_!). Actually it is my opinion that people dose way too much when they take any ammount of cocaine powder since cocaine is still active at just a few milligrams as it is found in Coca leaves. Therefore, cocain in its natural form is almost impossible to OD on.

I am willing to bet that MDPV is far more toxic than coke, simply due to its structural similarity to both Methcathinone and MDA, both of which are toxic. And although I know this is not a good reason, in my experience MDPV produces a more horrific aftermath for less euphoria when compared to cocaine.


----------



## Jamshyd

I'll be blunt: I think you _want_ MDPV to be non-toxic, just because you love it so much. I, too, _wanted_ dexamphetamine to be non-toxic when I was addicted to it. Well, guess what? yeah. These days I also _want_ Ketamine to be non-toxic because I use it medicinally in tiny doses (as you may have noticed in my posts). However, I have both historical and lab data besides my own experiece that proves that Ketamine is non-toxic. What do you have for MDPV besides theories? 

Almost nothing is known about MDPV. For all we know, it could be carcinogenic, or anything really. If you decide to keep using carelessly "untill some facts come to the contrary", then I am very afraid you yourself might become one of those facts. 

Please don't misunderstand me. I am saying all this out of concern for your safety, not as an attack.

As for coca evidence... erm, what do you mean by "non-anecdotal"? It is well known that people all over south america have been consuming coca as a primary part of their daily diet from time immemorial, and they still do today. There is something in wikipedia about that. I am currently too tired to search medical journals if that is what you mean, but for me, socio-historical evidence is even more sufficient than lab evidence (think of all the pathetic new researches popping up trying to prove that cannabis causes brain damage, for example).  

Contrary to Coca, MDPV has only existed for a couple of years. There is practically no historical evidence to show whether it is toxic or not.

And btw, keep in mind that one of the things that Dopamine degrades into is epineprine - so it is not really the NE affinity that determines cardiotoxicity (as you seem to be proposing) - it is actually the Dopamine's byproducts.

As for your question about my proposition that people take way too much coke, I already answered it: cocaine is active in just a few mgs. When people snort lines of hundreds of milligrams, they always risk a siezure. This means that when anyone snorts a line of coke they are flirting with an overdose.

And ps., the people in the andes are just as real as you are, and so are the _fin de siecle_ users of old .


----------



## fastandbulbous

> I am willing to bet that MDPV is far more toxic than coke



I'd not. If cocaine wasn't a local anaesthetic then that might well be the case, but all such drugs (lignocaine, procaine etc) have a cardiotoxic effect with prolonged or one off acute dosing because they interfere with transmission od the pacemaker signal across the heart. Add to that cocaine's effect on the sympathetic nervous system and it's short action that results in repeated dosing and you have a very dangerous drug. Ask any doctor in Florida or Texas (main routes into the US for coke) about the number of emergency admissions to casualty with cardiac related probems due to cocaine use, Cocaine is way more dangerous

BTW Jamshyd, I totally agree that most people take far too high a dose of cocaine when available as the alkaloid. If it was used as the coca leaf preparation there would be next to no fatalities from cardiac complications


----------



## qwe

earlier in this thread sydnocarb / mesocarb was being discussed

just FYI it's all over pubmed.  the general consensus of the research is that it is about half as powerful as d-amph and significantly less neurotoxic.  it's a dopamine reuptake inhibitor with a long half-life


----------



## everhopeful

*mesocarb info*

this is from a report done 1993 mainly concerned with metabolic precursor compounds that caused false positives i.e. you test positive for amphs without the pleasure of having taken one. i get the feeling it's a whole more subtle (read weak) than the amphs, and other reports i've read would confirm it's more of an "adaptogen with legs" than a straight stim.




			
				qwe said:
			
		

> earlier in this thread sydnocarb / mesocarb was being discussed
> 
> just FYI it's all over pubmed.  the general consensus of the research is that it is about half as powerful as d-amph and significantly less neurotoxic.  it's a dopamine reuptake inhibitor with a long half-life


----------



## everhopeful

does anyone have personal experience with amphetaminil (trade names amfetaminal, amfetaminyl, aponeuron, tonozwei, cas 17590-01-1).

"is an anorexic used to treat fatigue, depression and narcolepsy". reads well or maybe it's more a modafinil than amph type?


----------



## izo

iirc it is a prodrug for amphetamine. i guess it is in the same league with the other  n-substituted amphetamines (e.g. benzphetamine, fenethylline, fenproporex).
never had it but heard only good things about it. especially fenethylline seems to be a nice option.


----------



## toxide

I would like to know more about Pyridine based stimulants, if they might be any good or not.  I've seen many that at a glance look good and their cheap and available commercially, some examples would be...

2-(2-(Methylamino)ethyl)pyridine
2-(4-Methoxybenzylamino)pyridine
2-(Aminomethyl)pyridine
2-benzoylpyridine
2-diphenylmethylpyridine
3-(Pyrrol-1-ylmethyl)pyridine


----------



## MDPVagrant

nuke said:
			
		

> The duration for MDPV is about 2-4 hours.  MA usually last 7-10 or so (at least, for me).


Correct... MDPV *is* a 'happy medium' duration-wise, at least in my opinion.  



			
				General alcazar said:
			
		

> I disagree with MDPVagrant - MDPV is really in the reacreational meth substitute camp. Too compusive to use in low doses long term. Eventually it leads to higher, compulsive dosing in most if not all that take it. Sortof like using coke to get through the day. Works for a while, but eventually will get out of hand.


I don't recall exactly what I said originally, but let me put it this way : I personally cannot use most stimulants in utilitarian ways, even some that others insist are only good for that.  If it has the slightest effect on dopamine, I'm "in trouble" immediately.  So I do not claim to speak for anyone else -- it's up to them whether they're able/unable to use a stimulant non-compulsively, as well as how concerned they are about addictive behavior in the first place.  Some people have extreme problems even with caffeine, so who am I to judge.  

However, in terms of things like duration, specific effects and _apparent_ physical safety, I find MDPV 'promising' for utilitarian purposes, IF addiction can be avoided.  In other words, if MDPV were ever legitimized and prescribed for this purpose, I would support a joint doctor-patient decision as reasonable.   That's as far as I'll go.


----------



## General alcazar

MDPV is impossible for me to use in a utilitarian way. After 10 mg, the compulsiveness kicks in, and the stimulant effects are mild relative to the euphoria so any significant motivation would be fraught with distraction. It is good for euphoria, though. MDPV for me is a good way to waste an evening, or longer (I have a go to sleep every night rule - no binging on anything)...
I feel like if I need a motivator, I'll take more caffeine.


----------



## MDPVagrant

General alcazar said:
			
		

> MDPV is impossible for me to use in a utilitarian way. After 10 mg, the compulsiveness kicks in, and the stimulant effects are mild relative to the euphoria so any significant motivation would be fraught with distraction. It is good for euphoria, though. MDPV for me is a good way to waste an evening, or longer (I have a go to sleep every night rule - no binging on anything)...


A terrific regimen to follow, or so I discovered with my mice last time around.  Seven days straight of dawn to dusk dosing, WITH sleep and food, one full gram dosed -- _no psychosis, no paranoia, no nasty crash, no cravings_, nothing but some heavy egotism & a couple days of agitation & pissy mood afterward.  It's just amazing how much sleep/food helps in all departments, particularly in the sense of feeling more in control.  Almost miraculous.  

Quite a profound learning experience, and it helps immensely in my plans to design a (imo desperately needed) program to help addicts gain control back from stimulants, that one called "Regain-It" I'm now getting some real momentum going with!  If it works, I am going to get my 15 minutes of fame, maybe longer.


> I feel like if I need a motivator, I'll take more caffeine.


I agree... and suspect you misunderstood me previously.  I haven't used a stimulant as "motivator" *ever*, i.e. for studying or truck driving.  Not once in my life.  I just think MDPV may have potential in that area (including for ADHD), and am not ready to condemn it yet.  Many people's rats have tremendously more self-control than mine do, and MUCH less propensity toward compulsive/addictive behavior.  And -- many people's have it MUCH WORSE than my rats as well.  My tests have all been very much middle-of-the-road in that department.

Dopaminergic stimulants have a strong element of 'biological' compulsion.  But how deeply this affects people's behavior is totally psychological, and IMO can be learned/unlearned.  This area has been *totally neglected* by the treatment industry, and I am tremendously hopeful.  If anyone wants to see some preliminary "Regain-It" literature in MS Word format, drop me an Email or PM.


----------



## General alcazar

I disagree with MDPVagrant. I think that once someone discovers the euphoric side of MDPV, it is simply to distracting to do anything mundane. I used to find amphetamine, meth, ritalin and even BZP good to do studying, cleaning and other chores on. MDPV demands all one's hedonistic attention, though. I've wasted many an evening on the stuff. It's tricky, though, because the euphoria only seems present when one focuses on it. Of course, I have poor self-control..


----------



## MDPVagrant

General alcazar said:
			
		

> I disagree with MDPVagrant. I think that once someone discovers the euphoric side of MDPV, it is simply to distracting to do anything mundane. I used to find amphetamine, meth, ritalin and even BZP good to do studying, cleaning and other chores on. MDPV demands all one's hedonistic attention, though.


Weeee... even after I say this:


> I haven't used a stimulant as "motivator" *ever*, i.e. for studying or truck driving. Not once in my life. I just think MDPV may have potential in that area (including for ADHD), and am not ready to condemn it yet.


In other words, you DO condemn it for this purpose, for everyone, for all time (which is the only thing I'm not doing)?  SMART!  

You must have conducted numerous double-blind scientific tests, eh...  I'd love to see the results of your authoritative dismissal of MDPV as utterly unusable for non-recreational purposes (what is that, twice in a row now you've gone out of your way to disagree, no matter how much I qualified my statements... or is it three times in a row?).  Please share your research methodology and results.

Also, I'd like to know why a chemical so similar in structure and pharmacological profile to Ritalin would fail utterly for ADHD, while Ritalin has been THE drug of choice to treat this disorder?  Aside from yet another iteration of your own experience (one single human being in 6.6 billion), do you have some thoughts to add here?


----------



## vecktor

MDPVagrant

Also said:
			
		

> different folks different strokes.. might work as a motivator for some, others not ritalin is the same, some find it to be useless as a motivator and concentration improver. amp works as a motivator in many people but I find it to be too distracting.  I find modafinil at 400mg to be more useful simply because it gives an extra 4 hours in the day without any major price to pay.
> though money is a better motivator
> 
> Interesting the ADHD activity of ritalin and analogs seems to correlate with NE rather than DA and experiments that blocked the DA action didn't reduce the ADHD model in the rats..


----------



## MDPVagrant

vecktor said:
			
		

> Interesting the ADHD activity of ritalin and analogs seems to correlate with NE rather than DA and experiments that blocked the DA action didn't reduce the ADHD model in the rats..


Interesting, although MDPV gives me INCREDIBLE focus... I can literally sit and focus on a single activity on the computer for 8 hours straight without a break.  Not that it would necessarily work the same way for ADHD (which I don't have) but it seems to make sense that it could.


			
				vecktor said:
			
		

> different folks different strokes.. might work as a motivator for some, others not ritalin is the same, some find it to be useless as a motivator and concentration improver.


That's basically all I was getting at, that there's a possibility MDPV could work well for some people (particularly in a gradual dosing form, such as extended release tablets).  Nobody's going to be snorting, plugging or injecting it if it were prescribed for ADHD, and these rapid dosing methods probably contribute a great deal to compulsivity and overall addictiveness.  

But of course I could be wrong, and maybe everyone who touches it ends up addicted... tests would have to be performed, of course.  Clearly all just speculation otherwise.


----------



## hussness

If I could be confident about purity and long-term effects I might use it for my ADHD.  I've been prescribed methylphenidate, adderall, strattera, none of them work great for me.  I would've definitely tried modafinil, if I could afford it.  From the sound of it MDPV could be a good ADHD drug, it would just take a hell of a lot of money to get approval.  Even then I'm sure it would still end up schedule II, and it's probably a lot easier just to extend adderall patents by tacking on an amino acid.


----------



## Smyth

I have an excellent contact for modafinil. 
I am really skint atm, but the price for this is cheap by normal peoples standards.


----------



## Mal hyde

what about bk-PMMA ...


----------



## hussness

Considering the toxicity of PMA using it as a lead compound probably isn't such a good idea.


----------



## MattPsy

The beta-ketone may reduce affinity for 5-HTT (as seems to be the trend for it with such simple amphetamine compounds), and so reduce the potential toxicity. I've no idea what the bk would do to it's ability to inhibit MAO, though.


----------



## hugo24

Its a known compound,and I liked it:

http://www.bluelight.ru/vb/showthread.php?t=261562&highlight=methedron


----------



## stirfry

^you ever end up doing that 100mg dose hugo24?


----------



## Mal hyde

sounds exciting, i want some, makes perfect sense that it should do what it does .


----------



## haribo1

Wouldn't the 3 methoxy analogue be better?


----------



## nuke

the dichlorinated desoxypipradrol should be very easy to make and probably more potent than the parent compound, right?  that might get into the microgram range for a stimulant.

maybe a little on the long side, though..

also what about n-methylation or other substitutions on the piperidine ring to bring down the duration some?


----------



## vecktor

nuke said:
			
		

> the dichlorinated desoxypipradrol should be very easy to make and probably more potent than the parent compound, right?  that might get into the microgram range for a stimulant.
> 
> maybe a little on the long side, though..
> 
> also what about n-methylation or other substitutions on the piperidine ring to bring down the duration some?



dichlorinated both on the same phenyl or one chloro on each? I would expect both to be active, with possibly the 3,4 being more potent than the 4 4'


----------



## nuke

vecktor said:
			
		

> dichlorinated both on the same phenyl or one chloro on each? I would expect both to be active, with possibly the 3,4 being more potent than the 4 4'



I was thinking both benzene rings para-chlorinated (since it's more easily made), but i'd guess the 3,4dicl would be even more potent

if there was a subsitution on the piperidine that would allow for easier metabolic attack we might really be onto something lasting reasonable long, being fairly potent, and cheap

i guess the same goes for substitution of methylphenidate -- what about a lactone in place of the acetate group (to avoid scheduling)?


----------



## dbailey11

Someone compile alist of all the _good_ possibilities so I can go shopping.


----------



## fastandbulbous

nuke said:
			
		

> I was thinking both benzene rings para-chlorinated (since it's more easily made), but i'd guess the 3,4dicl would be even more potent
> 
> if there was a subsitution on the piperidine that would allow for easier metabolic attack we might really be onto something lasting reasonable long, being fairly potent, and cheap
> 
> i guess the same goes for substitution of methylphenidate -- what about a lactone in place of the acetate group (to avoid scheduling)?



Even easier, replace the methoxycarbonyl group of methylphenidate with an alkoxy or alkyl group. Apparently replacing said group with a propyl group gives a decent compound according to one paper I read


----------



## Dr.Heckyll

fastandbulbous said:
			
		

> Even easier, replace the methoxycarbonyl group of methylphenidate with an alkoxy or alkyl group. Apparently replacing said group with a propyl group gives a decent compound according to one paper I read


That paper must have been J. Med. Chem. 2007, 50, 219-232. However, they made the 4-chloro propyl derivative, which was characterized as a slow-onset, long-duration stimulant, potentially suitable as therapeutic for cocaine abuse. But that's not what you wan for recreational purposes.


----------



## almost-

https://rikki.fi/tajkor/bl/stim.jpg
https://rikki.fi/tajkor/bl/stim2.jpg
https://rikki.fi/tajkor/bl/stim3.jpg

*Source:*
Designer drugs directory / Karel Valter and Philippe Arrizabalaga. Published/Created: Amsterdam ; New York : Elsevier, 1998. Description: 212 p. : ill. ; 25 cm. ISBN: 044420525X


----------



## fastandbulbous

^ The first one is effectively phenmetrazine, but with a 5-membered heterocyclic ring. The second I assume id N,N-dimethylamphetamine, which is a pretty poor stimulant in comparison to amphetamine/methamphetamine.

Not sure if the last one refers to 4-fluoromethamphetamine or alpha-ethylphenethylamine, but I've talked to a friend who's had 4-fluoromethamphet and he said ir was OK, but nowt too special. As for alphaethylphenethylamine, my personal experience with it indicated it was a stimulant, but nowhere near as strong as that article states. By adding a beta-keto group, you get about the optimum side chainchain lenth cathinone derivative (for dopamine/noradrenaline reuptake inhibition).  Once you get a 5 carbon sidechain (eg like MDPV) 
the action becomes more dopaminergic & less noradrenergic.

My hope actually lies in 2-phenylcyclopentylamine & the N-alkylated derivatives  . Effectively a sort of incomplete fencamfamine (it has one of the alicyclic rings found in the structure of fencamfamine) with what seem to be similar effects


----------



## almost-

fastandbulbous said:
			
		

> As for alphaethylphenethylamine, my personal experience with it indicated it was a stimulant, but nowhere near as strong as that article states. By adding a beta-keto group, you get about the optimum side chainchain lenth cathinone derivative (for dopamine/noradrenaline reuptake inhibition).  Once you get a 5 carbon sidechain (eg like MDPV)
> the action becomes more dopaminergic & less noradrenergic.



Can you please say any references so that I could check more about SAR of that kind of compounds?

A very well respected person in that forum that disappeared in year 2004 said that his favourite stimulant was alpha-ethylphenethylamine:
"The only compound that helps me from not falling asleep during the morning (I sleep an average of 4-6 hours a night and it sometimes asks its toll) is modafinil. 150 - 200 mg in the morning helps, but it does not do more that keep you awake, it doesn't motivate me to do things.
Methamphetamine is a bit too strong for an all-around stimulant for me, like you said the euphoria is counter-productive when more motivation is the goal.
Probably the best stimulant I've tried, for both being awake and motivated without euphoria and maniac behaviour, is phenyl-2-aminobutane. it is useful as a study aid."



> My hope actually lies in 2-phenylcyclopentylamine & the N-alkylated derivatives  . Effectively a sort of incomplete fencamfamine (it has one of the alicyclic rings found in the structure of fencamfamine) with what seem to be similar effects



Do you have any SAR also about that kind of stimulants? Thanks.


----------



## fastandbulbous

For the first one, I'll have to dig about, but if you ghave access to pubmed you'll probably find them before me. As to the latter, it's just intuition on my part. Look up cypenamine (approved name for 2-phenylcyclopentylamine) for info on it's pharmacology.

You could just look up the Ki values (for DAT, NERT & SERT) of say cathinone, 2'-aminobutyrophenone, 2'-aminovalerophenone etc


----------



## almost-

Some pdfs from my collection:
https://rikki.fi/tajkor/SAR_of_stimulants.rar


----------



## ziddy

almost- said:
			
		

> Some pdfs from my collection:
> https://rikki.fi/tajkor/SAR_of_stimulants.rar


Link doesn't seem to work.


----------



## ralf2

almost- said:
			
		

> Some pdfs from my collection:
> https://rikki.fi/tajkor/SAR_of_stimulants.rar



This is interesting... I found within this .rar the file Handbook of Psychopharmacology, Vol 11 Chapter 1 Amphetamines Structure-Activity Relationships.djvu. On page 9 we find a table about the effect on N-alkylation of amphetamine on the potency. The very same table has been posted as an image here on bluelight several times.  However!, the data in the tables don't match. Someone must have changed the image! For example, in the one from the book ethylamphetamine is given as 60% of amphetamine, in the image 90%.

Compare:
The file: http://www.megaupload.com/se/?d=MNE0GM19 
The image: http://img118.imageshack.us/img118/682/alkylamfetaminertg7.jpg


----------



## LuxEtVeritas

^^^

are these potencies relative to Total AUC?


----------



## WarrenZevon

*Win 35065-2?*



			
				fastandbulbous said:
			
		

> ^ The first one is effectively phenmetrazine, but with a 5-membered heterocyclic ring. The second I assume id N,N-dimethylamphetamine, which is a pretty poor stimulant in comparison to amphetamine/methamphetamine.
> 
> Not sure if the last one refers to 4-fluoromethamphetamine or alpha-ethylphenethylamine, but I've talked to a friend who's had 4-fluoromethamphet and he said ir was OK, but nowt too special. As for alphaethylphenethylamine, my personal experience with it indicated it was a stimulant, but nowhere near as strong as that article states. By adding a beta-keto group, you get about the optimum side chainchain lenth cathinone derivative (for dopamine/noradrenaline reuptake inhibition).  Once you get a 5 carbon sidechain (eg like MDPV)
> the action becomes more dopaminergic & less noradrenergic.
> 
> My hope actually lies in 2-phenylcyclopentylamine & the N-alkylated derivatives  . Effectively a sort of incomplete fencamfamine (it has one of the alicyclic rings found in the structure of fencamfamine) with what seem to be similar effects





The first hand reports I have of found for 'WIN-35065-2' seem unrivaled.

I will be more specific.

CAS: # 74163-84-1

Chemical Formula: C16H21NO2

Synonyms:
2-beta-carbomethoxy-3-beta-phenyltropane,
(-)-2β-Carbomethoxy-3β-phenyltropane,
(beta-CPT)

Other names:
Troparil?

Thanks for any direction in advance!

- Zevon


----------



## haribo1

You mean this?






I was under the impression that para-halogens on the benzene ring made them a lot stronger? P-f seems the most potent...


----------



## Reminisant B

Feprosidnine (sydnophen)

http://en.wikipedia.org/wiki/Feprosidnine

Looks to be the simpler analogue of mesocarb. 

Possibly multiple modes of action.


----------



## Ham-milton

"opioid effects" eh?  All in all, it sounds pretty good.


----------



## LuxEtVeritas

as a highly realted substance to mesocarb it may also "lack abuse potential" which usually means rec potential


----------



## WarrenZevon

*Safe Ligand at C17H21NO4 sites!*



			
				haribo1 said:
			
		

> You mean this?



YES!

RAVE reviews!

http://en.wikipedia.org/wiki/%28-%29-2β-Carbomethoxy-3β-phenyltropane

http://en.wikipedia.org/wiki/%28-%29-2β-Carbomethoxy-3β-phenyltropane

Just like C17H21NO4 - but much longer lasting and stronger!

How do you get this stuff?


The first hand reports I have of found for 'WIN 35065-2' seem unrivaled!


Chemical Formula: C16H21NO2

Synonyms:
2-beta-carbomethoxy-3-beta-phenyltropane,
(-)-2β-Carbomethoxy-3β-phenyltropane,
(beta-CPT)

CAS: # 74163-84-1

Thanks in in advance!

- Zevon


----------



## haribo1

Mesocarb (and sydnophen) look like interesting compounds, at least interesting enough to appear in the MoDA & DEA scheduling.

Looks interesting, but how to form a mesoionic sydnone imine? I've never come across them before now. Interesting...


----------



## MattPsy

WarrenZevon: If you have user reports of CPT, please link them.
I'm interested.


----------



## Reminisant B

out of interest do you think 2β-Carbomethoxy-3β-phenyltropane would form the same equivalent analogue of cocaethylene when mixed with alcohol?


----------



## LuxEtVeritas

^ yes likely it would coorespond similarly


----------



## WarrenZevon

Try:

http://groups.google.com/group/alt....d54eaf6e?lnk=st&q=WIN+36,065#222a7804d54eaf6e

http://groups.google.com/groups/sea...AAkeBMm6r5vxwuPAe_D6fX8OPANdqfI6prRsqjc7uCt1A


On Apr 15 2005, 2:58 pm, "MobiusDick" <MobiusD...@gmail.com> wrote:
> LOL
> 
> Sounds Cool to me.  A lot of the drugs I work with have only numbers
> associated with them. For example (and I have not worked on this for
> years) WIN 36,065; SKF 28,175; SK882; or MK-801.  WIN 36,065 is the
> best cocaine analogue you will ever do (IMHO) It is an amazing drug.
> But I do not work as much with DA reuptake inhibitors these days.
> 
> I would like to be able to name a drug, like the guys who named the
> endogenous marijuanna receptor (CB-1)  ligand anandamide after the
> Sanskrit word for bliss Ananda.
> 
> Mobi


----------



## WarrenZevon

*Dimethocaine? HOW ELSE CAN I SPIKE / IMPROVE  MY Street C17H21NO4?*

Legal and supposed to work "like cocaine"; Dimethocaine.

Dimethocaine
C16H26N2O2
(CAS) 94-15-5

(3-diethylamino-2,2-dimethylpropyl) 4-aminobenzoate
OR
1-Propanol, 3-(diethylamino)-2,2-dimethyl-, paminobenzoate (ester)

Is 'supposed' to work like cocaine.
But no human reports and
WE DO NOT DISCUSS VENDOR TYPE THINGS AT ALL, OK?


----------



## fastandbulbous

^ Personally, I think that the local anaesthetic activity is a bad thing as it massively increases cardiotoxicity. The above tropanes without local anaesthetic activity are a much safer bet IMO


----------



## LuxEtVeritas

Yes the methocaine is an anesthetic in line with other 'caines, so in that regard it is not optimal
however, IMO as to US law at least if we are to look at that aspect the tropanes largely can be considered analogues whereas methocaine as i can see is really not substantially similar to any Sched I or II compounds, namely of course cocaine

?????

for you in Britain i guess you can have your tropane analogues, lucky blokes


----------



## Ham-milton

Without going into the synthesis, how difficult would something like this be to make?


----------



## LuxEtVeritas

At issue may be what is the potency of dimethocaine (DMC) as an anesthetic in relation to cocaine (C) and in relation to its potency at DAT et al

as i would estimate DMC likely requires a dosing of ~5x C, so if it is equal in its anesthetic potency than cardiotoxicity is heightened 5x as well due to requisitie dosing

if so not good is suspect....

anyway anyone also care to speculate of the SAR of cocaine and other tropnae DAT analogues and how that all matches up with the effect DMC (an other anesthetic 'caines) have at DAT....?

obviously DMC was not designed to be a DAT inhibitor so other like structures may be preferential for DAT and less so for anesthetic potency


----------



## LuxEtVeritas

ok...methinks i have an idea....


----------



## fastandbulbous

After trying pseudotropyl 4-fluorobenzoate, I'd say that it's a much better bet as long as you don't live somewhere with those draconian analog act pieces of legislation. Almost no local anaesthetic activity and around a third the potency of cocaine. Add that to it's much, much easier synthesis and voila, a winner.

It's a shame really that cocaine (and the above mentioned fluorotropacocaine) turn me into an egotistical wanker arsehole of the first order...


----------



## Ham-milton

unfortunately most of us live under draconian analogue acts (okay, maybe not draconian, just poorly written).

In one study, I found that tetracaine (amethocaine) substituted for cocaine just below dimethocaine (has a monomethocaine been tested?) and above lidocaine and another *caine derivative.

Since amethocaine is a commercialized product, it'd be easier for 99% of the world to come by.  Aside from it's anaesthesia, how likely is this to be significantly recreational?


----------



## LuxEtVeritas

i have seen that as well but did not see the relative potency ratio and since DMC may be as low as 1/10 of C this may be an order of magnitude lower than that even for argument sake and that would be quite low and require huge doses to get anywhere and likely again as stated you may have high cardiotoxicity at those levels which is not a pretty thing

probably looking at minimally 500mg and that is at best if at all

even Procaine was shown to be strong at DAT but had no abiltiy to sub for C at any rationale dose


----------



## LuxEtVeritas

CFT is 1/3 potency of C, ...what is CPT?


----------



## MattPsy

CPT is CFT minus the p-fluoro substituent on the phenyl ring.


----------



## mad_scientist

CFT is 7x the potency of cocaine (in rats at least), but much longer lasting;

Norman AB, Buesing WR, Norman MK, Tabet MR, Tsibulsky VL. The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination half-life in rats. European Journal of Pharmacology. 2004 Jan 12;483(2-3):281-7.

Pseudotropyl 4-fluorobenzoate is the analogue of cocaine with the 2-COOCH3 group removed and the benzene ring substituted with fluorine at the 4-position, so similar to CFT in some ways but much less potent.

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5147770


----------



## hussness

*Intramolecular H-bonding in phenyltropane and methylphenidate DRIs*

I have recently read and thought a bit about the intramolecular H-bonding theory that attempts to unify the SARs of methylphenidate and phenyltropane cocaine analogs, and have drawn some structures.  I was wondering if anyone would mind checking them and commenting on whether or not they are consistent with the theory.


----------



## fastandbulbous

mad_scientist said:
			
		

> CFT is 7x the potency of cocaine (in rats at least), but much longer lasting;
> 
> Norman AB, Buesing WR, Norman MK, Tabet MR, Tsibulsky VL. The self-administration of WIN 35,428 and cocaine: comparisons of satiety threshold and elimination half-life in rats. European Journal of Pharmacology. 2004 Jan 12;483(2-3):281-7.
> 
> Pseudotropyl 4-fluorobenzoate is the analogue of cocaine with the 2-COOCH3 group removed and the benzene ring substituted with fluorine at the 4-position, so similar to CFT in some ways but much less potent.
> 
> http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5147770



May be 7x the potency in rats, but from personal experience with CFT ( had 500mg given asd a gift from a friend to 'play around with') it's at most 2x the potency of cocaine ih humans and is qualitatively different in feel (more like methylphenidate in feel), being less euphoric. 

While less potent in terms of dose required (25mg of fluorotropacocaine vs. 5mg of CFT), fluorotropacocaine felt very cocaine-like. From people I know who've also had both and are fans of cocaine (I'm not), CFT was not seen as a suitable replacement whereas some preferred fluorotropacocaine to their street bought coke...


----------



## LuxEtVeritas

FnB had intimated CFT at 1/3 C and i was asking what ratio of potency is CPT to C, not what it was (or trying to commuinicate that ,LOL)

also i see now he has noted perhaps at most 2x potency of C in humans

anyway it also appears to not be as 'good' qualitative to aficionados i guess

also what is the ratio of TropaC to FlurotropaC?


----------



## Thanatopium

4-MAR is long acting to say the least, and takes a heavy toll on the body IMHO.  Plain old aminorex should be rated as far more euphorigenic than methamp or even cocaine.  Body rushes, the works.

There is a strange "flavor" to these compounds... The serotonergic effects are terrifying.  VERY subtle at first, OCD behavior begins, ending in a completely pathological schizotypal state the user is completely unaware of.  

I would not hesitate to say that they are smart drugs in the truest sense of the word.  But the same effects that make them nootropic at low doses and well maintained rate of ingestion become the elements of the psychosis...  

Intuition of interconnected concepts, sensitivity to the moods, emotions, and intentions of others, laser like mental focus...  

Easily I would say they have more of an elemtn of risk than methamp, because even the most self aware, educated user is taken off guard...

A beautiful, terrifyingly seductive set of compounds.


----------



## bupropion

Riemann Zeta said:
			
		

> Also, I dug up an old (2003) review article by Rothman & Baumann (link below) that had EC50 values of neurotransmitter release (not reuptake, but truly release) for a number of phenethylamines (all in nM):
> 
> Phenethylamine:                5-HT; NA; DA
> 
> (d)-amphetamine:               1765; 7.07; 24.8
> 
> (d)-phenmetrazine:             3246; 37.5; 87.4
> 
> (d)-methamphetamine:       736; 12.3; 24.5
> 
> (d)-fenfluramine:                 51.7; 302; 10000
> 
> (dl)-MDMA:                          56.6; 77.4; 376
> 
> Rothman & Baumann (2003). Eur. J. Pharmacol. 479: 23-40.




Do you have the EC50 values for methylphenidate, cocaine, meth/cathinone, and any of the stimulant diet drugs for comparison?

Edit: I found a chart but it doesn't have values for methylphenidate, methcathinone, mephentermine or 4-methylaminorex, norpseudoephedrine or MDPV.  Also it gives extremely high values (>10,000) across the board for diethylpropion (?).


----------



## bupropion

What would amphetamine with a double bond to the methyl carbon do?  Is there any possibility it would be stronger?


----------



## Ham-milton

You're really interested in really tiny changes to the structure.

Doubt it'd be stronger.


----------



## haribo1

bupropion said:
			
		

> What would amphetamine with a double bond to the methyl carbon do?  Is there any possibility it would be stronger?



It would be an imine which is a)much less basic & b)is unstable.


----------



## Riemann Zeta

> What would amphetamine with a double bond to the methyl carbon do? Is there any possibility it would be stronger?



You mean this?  I think it would be inactive, considering the conformational lock that an sp2 carbon engenders.  Also, it would be pretty unstable; it would polymerize rather quickly.  Might be a good synthetic plastic.


----------



## Smyth

*Olefinic alkaloids*

It's actually called an olefin, an imine is the name for when the double bond is connected to the nitrogen.

Im not sure if it would be that stable, but it's related to F&B's original proposal for PEA-based psychedelic.

The N-benzyl psychedelics have incredibly potent _in vitro_ activity.

You'd also have to think about how this olefinic compound could be made. In the synthesis of selegiline the α-carbon originally starts life as: 

Carboxylic acid -> 1° alcohol -> alkyl-chloride -> methyl

F&B's original proposal actually was for compounds possessing a β-methylene functional group, before anybody tries to correct me.

However, in order for the _terminal_ olefin to be _relatively_ chemically/metabolically stable then it must be conjugated to something, such as an oxgen in the specific case of the allyloxy group. 

A vinyl group stuck connected to a phenyl ring is okay though because of the resonance with the aromatic electrons.


----------



## Pomzazed

Oops, double bond at that position will quickly undergo tautomerization from its enamine form to the more stable imine form.






where in the condition where water is present, the imine would be further hydrolyzed to 1-phenylpropan-2-one and ammonia.


----------



## Holy_cow

Smyth said:
			
		

> In the synthesis of selegiline the α-carbon originally starts life as:
> 
> Carboxylic acid -> 1° alcohol -> alkyl-chloride -> methyl



Selegiline is nowadays exclusively made from ephedrine, which has the advantage of being stereospecific.


----------



## bupropion

Isn't the ephedrine sold in stores the l-isomer and pseudoephedrine the d-isomer?  Could d-deprenyl be synthesized by starting with Sudafed?  What about adding a hydroxy group at the beta position to selegiline, then synthesizing d-deprenyl from that?


----------



## Smyth

Pomzazed, good observation my friend! I had entirely overlooked that simple yet entirely fundamental bit of organic chemistry. Well spotted!

I have a paper on d-selegiline somewhere. Due to the fact that it is metabolized to the active isomer of meth, they wanted to see what the abuse value of this was like, comparing to the levo-isomer.

The synthesis from L-phenylalanine is also completely stereospecific too. I dont judge selegiline to be a worthwhile drug imo. Some guy said his friend was taking Emsam and found it helpful. Selegiline is cheap though, its just the customs charge (£12) meant my original order including delivery (£18 ) meant that it almost doubled in price. I thought it was a big let-down, since I had got quite high hopes that a compound which increases the amount of neuronal dopamine would be a very worthwhile substance, especially given its high potency. However, I stopped taking it before even getting half-way through my script of 100 tablets.


----------



## fastandbulbous

bupropion said:
			
		

> Isn't the ephedrine sold in stores the l-isomer and pseudoephedrine the d-isomer?  Could d-deprenyl be synthesized by starting with Sudafed?  What about adding a hydroxy group at the beta position to selegiline, then synthesizing d-deprenyl from that?



l-ephedrine & d-pseudoephedrine both have the same stereochemistry surrounding the carbon with the amine group (both get reduced to d-methamphetamine). Deprenyl has the opposite stereochemistry about the amine carbon (it's metabolites are l-methamphetamine & l-amphetamine) so they'd start with d-ephedrine or l-pseudoephedrine)


----------



## bupropion

Pomzazed said:
			
		

> Oops, double bond at that position will quickly undergo tautomerization from its enamine form to the more stable imine form.
> 
> 
> 
> 
> 
> 
> where in the condition where water is present, the imine would be further hydrolyzed to 1-phenylpropan-2-one and ammonia.



Would the imine form be active?  How much so?

\/ Oops, sorry for not reading/thinking at the time.


----------



## vecktor

bupropion said:
			
		

> Would the imine form be active?  How much so?



the answer is in the bottom part of the post you quoted above.


----------



## <pyridinyl_30>

P2P is not active.


----------



## Vivian

I wish this thread could be translated for people who are not chemists.


----------



## kaskelot

I don't.

It spurs me to study harder those resources that I have access to, and indulge in more and more of journal articles and my own experience of both stimulant and psychedelic psychoactives.


I consider desoxypipradrol fantastic as a stimulant, but I'm a bit weary about the tolerance and possible negative effects of that tolerance in the long run. Is there substances of the same subjective character, or any possibility to limit tolerance gaining from desoxypipradrol? I'd consider it an old stimulant of future importance if it can be handled safely.


----------



## Riemann Zeta

I've never had the pleasure of trying desoxypipradol as I've never encountered it.  It is very potent and quite long lasting.  I think people really overdo it dosewise--considering that it is active at around 2mg, a good dose should be under 5mg, taken only in the early morning (like an ICBM under your ass).  Obviously, people taking 10-20mg of it several times a day are going to have insane problems with insomnia.

If you want a desoxypipradrol analogue that is shorter-acting, try pipradrol itself.  The hydroxyl group doesn't dramatically weaken the stimulant effect, but it does give the body an easy metabolic target for conjugation/elimination.  But good luck finding pipradrol, it is even rarer than its desoxy brother.


----------



## MattPsy

The synthesis is pretty easy, the piperidine acid chloride + diphenyl grignard should work.
It's amazing it doesn't crop up more actually . (pipradrol)


----------



## vecktor

^ I think it is more likely to be indirectly made from chloromethyl pyridine plus the diphenyl ketone, benzophenone then reduction of the pyridine ring.


----------



## bupropion

*The effect of adding specific elements or grups to benzos*

Oops, wrong thread


----------



## haribo1

Thanatopium said:
			
		

> 4-MAR is long acting to say the least, and takes a heavy toll on the body IMHO.  Plain old aminorex should be rated as far more euphorigenic than methamp or even cocaine.  Body rushes, the works.



I've tried 4MAR and I liked it a lot. I took 50mg in the morning (about 10am) and it seemed to wear off at about 10pm so that's 12 hours. It felt more entacogenic than amphetamines, it was like a low dose of MDMA with some methamphetamine but it had fewer physical effects.

How does  'plain' aminorex compare on dosage and duration? How much is it wise to take? I'm wondering about the sreies because, for example, the p-F analog is supposed to be almost 5 times more potent than the parent (1.2mg/kg as opposed to 5.8mg/Kg).

With (meth)amphetamines, the p-F analog is slightly less potent. I am beginning to think that the aminorex skeleton doesn't work like amphetamines. I suspect it might be a dopamine & norepinaphrine reuptake inhibitor...

I think with it's similar structure to amphetamines, people have assumed that it's action is similar. I  am becomming more & more certain that it's not...


----------



## NeuronalPerception

Armodafinil and Rasagiline I expect to try out shortly. I currently use deprenyl and modafinil as needed as a stimulant.


----------



## Riemann Zeta

Ooh, cool.  I'd like to try (R)-modafinil to see how it compares to the original.  Intuition tells me that there would be almost no difference--the (R)-enantiomer as a drug is most likely just a patent-extending strategy by Cephalon in the wake of decent generic modafinil (I hope that is available soon).


----------



## Holy_cow

*Morpholino-Pipradrol*

It was debated what effect the pipradrol analogue with a morpholine ring instead of the piperidine ring would have. Here is a patent describing this compound: US 2'947'749.


----------



## <pyridinyl_30>

bk-2-benzylpiperidine and bk-2-piperonylpiperidine are two easy (1-step reaction) targets which have not, to my knowledge, been bioassayed as of yet.  Also, 
bk-3-benzylmorpholine and bk-3-piperonylmorpholine.  

So many drugs, so few resources.


----------



## fastandbulbous

Holy_cow said:
			
		

> It was debated what effect the pipradrol analogue with a morpholine ring instead of the piperidine ring would have. Here is a patent describing this compound: US 2'947'749.



Most potent of the series (applies to both pipradrol & desoxypipradrol morpholine derivatives); think the DAT affinity was 50% greater for the morpholine compared with desoxypipradrol. What I've been wondering is if the morpholine derivative been the most potent heterocyclic wouls also work for drugs with a single aromatic group (eh methylphenidate)


----------



## kaskelot

Riemann Zeta said:
			
		

> I've never had the pleasure of trying desoxypipradol as I've never encountered it.  It is very potent and quite long lasting.  I think people really overdo it dosewise--considering that it is active at around 2mg, a good dose should be under 5mg, taken only in the early morning (like an ICBM under your ass).  Obviously, people taking 10-20mg of it several times a day are going to have insane problems with insomnia.
> 
> If you want a desoxypipradrol analogue that is shorter-acting, try pipradrol itself.  The hydroxyl group doesn't dramatically weaken the stimulant effect, but it does give the body an easy metabolic target for conjugation/elimination.  But good luck finding pipradrol, it is even rarer than its desoxy brother.



In the country I'm currently residing, Sweden, it seems like the overdoing is quite abundant among those who like desoxypipradrol. Doses from 10 mg upwards are frequently reported in some of the larger drugrelated forums, as well as redoses as soon as a few hours from first dose. 

I'm fond of the long-acting properties of desoxypipradrol, it's kind of nice to have a full 24hrs of an alert and waken state of mind, on two dosings, 2+4 mgs seven hours apart, with no negative aftereffects as far as I've noticed the six times I've done it. It seems like I need three to five weeks without stimulants of the same charater, DAT-inhibiting &c., for the tolerance to lower, but it's hard to determine whether it actually drops since the desoxypipradrol is so subtle.


----------



## <pyridinyl_30>

fastandbulbous,
I'm quite sure that the morpholine analogue of methylphenidate (which I'm on right now) will be quite a bit stronger than the parent compound.

Have them whip us up a batch!


----------



## mr shush

Wasn't desoxypipradrol in them legal highs/not so legal high pills N@#@#@#@# ?


----------



## MattPsy

^ No. That was diphenyl prolinol.


----------



## haribo1

Anyone tried chasing desoxy like heroin? It has an effect right away & an actual rush... that lasts for 2-3 hours. I dunno about low doses, I've only ever taken 10mg+ at once...


----------



## NeuronalPerception

Riemann Zeta said:
			
		

> Ooh, cool.  I'd like to try (R)-modafinil to see how it compares to the original.  Intuition tells me that there would be almost no difference--the (R)-enantiomer as a drug is most likely just a patent-extending strategy by Cephalon in the wake of decent generic modafinil (I hope that is available soon).



I currently use generic modafinil. The R form is more potent and abit cleaner of a stimulant. There is a noticeable difference but perhaps not as strong as the different between R-Lipoic acid and ALA.


----------



## Hyperspace

I had came up with some new ideas for possible stimulants.

*1-(4-methylthiophenyl)piperazine (I would call this MeSPP)*

This is the sulfur analogue of MeOPP, where the methoxy group is replaced with a methylthio group.  Given the increase in potency as you go from PMA to 4-MTA, it's possible that MeSPP would be slightly stronger than MeOPP.  The only thing I can find regarding this analogue is listed here:

http://www.wipo.int/pctdb/en/wo.jsp?IA=WO2006094843&DISPLAYESC

The analogue is listed under "Description 40".

*1-phenethylpiperazine*

This one is similar to BZP in structure, but the benzyl group of BZP has been extended by an extra CH2.  The benzyl group can be represented as C6H5CH2, while phenethyl can be represented as C6H5CH2CH2.  It vaguely looks similar to phenethylamine, where a piperazine ring takes the place of the amino group.

Now for some possible non-piperazine based stimulants:

N-methyl-1-cyclopropyl-propan-2-amine
N-methyl-1-cyclobutyl-propan-2-amine

These two look similar to methamphetamine, except the phenyl ring has been replaced by a cyclopropyl and cyclobutyl ring respectively.  Since Cyclopentamine (cyclopentyl analogue) and Propylhexedrine (cyclohexyl analogue) are stimulants, the cyclopropyl and cyclobutyl analogues may also be stimulants as well.


----------



## Ham-milton

I'm sure they'll have some stimulant activity, but I sure as hell wouldn't touch them.  ick.

if propylhexedrine is migraine in a sniffer, I can't imagine what these would be like!


----------



## BongFish

Anyone know the legal status of 4-fluoro-4-mar in uk and elsewhere?


----------



## MobiusDick

*Stimulants Of Ahe Future Are Already Here*

While perusing some of the posts, I came upon this one and decided that I needed to chime in here. While there are certainly more than two classifications of non-entactogenic stimulants that are drugs of abuse in animal models --and yes that is important because you find individuals who abuse strange atypical drugs that very few people find pleasant-- let's just narrow it down for simplicity's sake and say that abusable stimulants basically fall into two classes based on their interactions with the DAT and the VMAT-2, and whether they have any direct activity themselves at the D2/D3/D4 receptor subtypes: stimulants of the cocaine type and stimulants of the amphetamine type.

Now of the stimulants of the cocaine type, some of the most pleasant compounds ever created have been around for decades, but are relatively complicated to produce due to their extensive chirality, so veritably a handful of drug users have ever tried them and the vast majority of drug users have not even heard of them.  These include WIN 35,065-2; WIN 35,428, RTI-121 and RTI-55. Of these, IME, There is no God but WIN 35,065-2 (let's call the others demi-gods.) Also note that none of these drugs lasts incredibly long, with some of them lasting perhaps three times as long as cocaine, but when the drugs last much longer, they tend to lose some of their euphoriant effect. I am not sure that this is absolute with cocaine analogues, but it does not seem to apply to amphetamine analogues: they can last for days.

If you look at the images in the Word doc, you will see all these cocaine analogues are phenyltropanes, but there are some very good analogues made from arecoline which substitutes the ubiquitous piperidine structure (which does appear on tropane if looked at in 3 dimensions.)

As far as amphetamine analogues, I have far less experience with these, but I do find 4MA (4-methyl-aminorex aka Euphoria) very pleasant along with derivatives of nomifensine and aminopropylferrocene . They are very pleasant but they still do not have the magic of cocaine type to me. Great amphetamine analogues that were not created by Sasha Shulgin (or at least synthesized by him) and are not entactogenic are difficult to come across. Most analogues are of lesser abuse potential than methamphetamine. If Shulgin had worked on cocaine analogues, I am sure we would have the equivalent of PIHKAL (Perhaps CAIHKAL. I have commented in the past on writing OIHKAL insofar as a definitive book on opioids, but it would be much more destructive, particularly with the way I tend to look at drug use lately. (i.e., I do not want anyone to die from a book like this which is why I doubt I would write one.)

If any of these compounds ever became widespread and easy to obtain, we would have "epidemics"  far greater than the so called meth or crack epidemics (Both aminorex derivatives and cocaine analogues would easily change most stimulant addicts drug of choice, of that I am certain, as I never did these drugs with anyone who did not start to nag me about doing more. I quickly learned to be careful who you share with. If they don't have respect for you, they will try to obtain these drugs at all costs. I know the drug in part has a hand, but the character is also an issue.

MobiusDick


----------



## vecktor

aminopropylferrocene, not only a stimulant but full of ferric goodness, mobius is this cyclopentadienyl iron compound what you mean, if so I am truly fascinated. tell me more.

most of the phenyl tropanes seem not to have too much potential. on the whole they are slow on long duration materials, though there are a few like troparil that mobius mentioned which are devastatingly effective, and a few ester and para substituted on the phenyl variants which have extreme speed of onset, better than cocaine with very effective DA raising abilities.


----------



## Pomzazed

^ Fe(cp)2 compounds seem to be toxic for cells? 
(interupt dna replication by joining two ends and blocking it from more replicating)


----------



## <pyridinyl_30>

*Cocaine analogues.*

According to Rhodium, the (-)-2-beta-carbomethoxy-3-beta-(3',4'-dichlorophenyl)-tropane analogue was shown to be most addictive / reinforcing in animal studies.

Interestingly, the DEA deleted the study's experimental procedure section!

About Nomifensine Analogues

I had never heard of this compound or seen its structure until just now, but I immediately wondered when I saw it what removing the anilinobenzo group would do. 

So is N-methyl-3-phenylpiperidine a known nomifensine analogue and have you tried it?
Even more interesting to investigate to me would be the activity of N-methyl-3-(3,4-methylenedioxyphenyl)-piperidine.  

Sorry if all this dopamine-mimicking, phenethylamine talk bores you, vecktor, it's what I like.


----------



## vecktor

I am not averse to stimulants, and I think the phenyl tropanes are very interesting as are fencamfamine and nomifensine. The phenyl tropanes are tedious to make unless one starts with cocaine and that defeats any legal advantage they have. RTI-55 p-iodophenyl methoxy carbonyl tropane  has been tasted in man, and was not found to be particularly interesting or worthwhile.

I am just bored with people just doing minor tweaks to known pea and tryptamine molecules and then thinking that it has never been thought of before, it has.............on numerous occasions. 

nomifensine has problems due to immune system reaction to it followed by hemolytic anemia, look up merital, hoechst. it appears that problems had emerged in trials but were ignored, though somehow hoechst didn't get sued out of existence over it.  All the evidence points to the mechanism of the toxicity being to do with the aniline moety stabilising the metabolically oxidised  tetrahydroquinloline, i have posted about it on this forum.
the substance without the aniline part would be N-methyl 3-phenyl piperidine, for some reason I do not like the look of this molecule, though it seems unlikely it will metabolically oxidise to a stable tetrahydyropyridine, the stabilising phenyl is in the wrong position, I just don't like the look of it- gut instinct I guess.

the related substance diclofensine made it some way through trials before being stopped, sometime in the early 80's. It appeared as a research compound through legitimate channels for a while.  diclofensine is one of the most effective substances at increasing extracellular dopamine levels through it is supposed DAT inhibition, and it also is very effective at inducing stereotypical behavior in rats.
next to nothing is known about its effects in man.


----------



## Biphasic

vecktor said:
			
		

> next to nothing is known about its effects in man.



That's not totally true;



> Double-blind comparison of diclofensine with nomifensine in outpatients with dysphoric mood.
> 
> Funke HJ, Holtmann W, Ismail S, Jansen W, Leonhardt KF, Muth H, Omer LM, O'Connolly M, Ramm H
> 
> Depressed outpatients (n = 107, age 26-75 years) were treated with either a 50 mg single morning dose of diclofensine (n = 54) or 75-100 mg nomifensine given in two divided doses (n = 53) over a period of three weeks. The baseline mean values of the Depression Status Inventory (DSI index) of Zung corresponded to those of a mildly depressed population, as given by Zung. At the end of the treatment the mean DSI and Anxiety Status Inventory (ASI-index) values of both groups dropped to the levels of a normal population. The side-effect profile of the two treatments was similar. There were no side-effects indicating sedation. Adverse effects of the anticholinergic type were rare. It can be concluded that both diclofensine and nomifensine are beneficial for the treatment of depressed outpatients and that in a dose relation of 2:3 (diclofensine:nomifensine) they lead to a similar improvement in depressive outpatients.



PMID: 3725890

Long term toxicity is still a big issue with this one, though.


----------



## <pyridinyl_30>

*Win 35,065-2.*

At 9,000 euros a gram, I don't seen Troparil aka WIN 35,065-2 aka 
(-)-2-beta-carbomethoxy-3-beta-phenyltropane becoming a widespread drug of abuse on the illicit or semi-illicit markets anytime soon.


----------



## Holy_cow

<pyridinyl_30> said:
			
		

> About Nomifensine Analogues



I was prescribed nomifensine as antidepressant when it was still on the market. It had little if any effect and certainly was not recreational.


----------



## Holy_cow

And not to forget: Indatraline, yet another potent DARI without recreational value.


----------



## <pyridinyl_30>

I didn't mean to imply that WIN 35,065-2 (3-beta-des-OC(O)-cocaine) doesn't have great abuse potential as has been reported but rather that is exorbitantly expensive when compared with other, similar drugs such as freebase cocaine, for instance.  

Of course, all of that could change instantly with the discover of a simpler, better, cheaper, easier and/or more elegant synthetic route leading to Troparil starting with atropine or some other inexpensive plant alkaloid and common industrial and/or over the counter reagents.

I wonder what the dosage range and estimated lethal dose 50 percent (LD50; a drug safety measure) for humans of this compound is?


----------



## Holy_cow

The chemistry of these compounds has been very well researched. There won't be no miraculous new route bringing down the price to an affordable range. Either you start with cocaine as precursor, or you make the precursor, but then you end up with a mix of isomers.

I don't think the tropanes are chemically/economically suitable for the RC market. Better look for dopamine reuptake inhibitors from other chemical classes.


----------



## Holy_cow

Nomifensin has the following Ki values for uptake in nM: DA 79, NE 3.8, 5-HT 874; diclofensin DA 14.6, NE 4.4; 5-HT 18.8; indatralin DA 0.99, NE 0.26, 5-HT 0.48. The indatraline values are from a different study, so might not be directly comparable. Not sure if anybody is interested in that, but I post it anyhow.


----------



## Holy_cow

As BZP surrogates I would suggest the following:
1-(2-Pyridylmethyl)-piperazine
1-(3-Pyridylmethyl)-piperazine
1-(4-Pyridylmethyl)-piperazine 
Some might even be commercially available, else they are easy enough to make. Replacing the aromatic ring with a 2- or 3-thienyl would be a further option. All that is just classic medicinal chemistry. Desoxypipradol with either one (best) or both (slightly less potent) phenyls replaced by 2-thienyl is still a potent stimulant. The corresponding thienyl-pipradrols (with OH) are only weakly active. So there's some unpredictibility in the SAR of these compounds.


----------



## Riemann Zeta

I've never even heard of this 'aminopropylferrocene' compound that is purported to be a stimulant.  Moreover, I don't really understand the chemistry of it: an organometallic ligand coordinated with Fe?  Not only does that sound like trouble for human cells, it also sounds like a highly improbable structure for a stimulant.  

Ferrocenes are used as a catalysts and molecular scaffolds in organic reactions, but I have never heard of one used as a pharmaceutical.  Is this the actual structure?  If it is, I think it would be mad toxic.


----------



## Pomzazed

^
I supposed that it just link to one cyclopentadienyl ring, not linked to both two.

Personally i think adding ferrocene doesnt attract me that much due to the fact that sandwich compounds tends to be cell destroying. (crosslink on DNA strands)


----------



## Holy_cow

<pyridinyl_30> said:
			
		

> bk-2-benzylpiperidine
> So many drugs, so few resources.


Don't know what the bk stands for, but 2-benzylpiperidine has been scientifically tested and found to be a very weak DA reuptake inhibitor (IC50 8.8 µM). It was also practically inactive at the other uptake sites.


----------



## Riemann Zeta

^^ Bingo.  Sounds carcinogenic.  I certainly wouldn't ever want to ingest an organometallic psychopharmaceutical.


----------



## clonazepom

I would  love to see new stimulant come out that relases serotonin and dopamine like the way meth does
 in Depot form tablets that start from 100% relase decreasing each day in 7 days and you'd get no come down at all.
Wouldnt hurt if it relased all serotonin the way mdma does, but kept the high going on for as long as you wanted..

For what purposes it'd be created? Happines.. but thats not possible becuz it would destroy your brain in matter of months, in reality.

WTF Im talking about? Gotta go bed now.


----------



## Holy_cow

^A compound with similar properties to your pill has been created:N-methylindatraline: Slow-Onset, Long-Duration 3-(3',4'-Dichlorophenyl)-1-indanamine Monoamine Reuptake Blockers as Potential Medications To Treat Cocaine Abuse._ J. Med. Chem. 2000, 43, 4981-4992._ A high dose will last several days. The lasting stimulantion and lack of sleep might not be too good for your mental health.


----------



## Riemann Zeta

> A high dose will last several days. The lasting stimulantion and lack of sleep might not be too good for your mental health.


Can't sleep...clown will eat me.  

I only take long-acting stimulants (or extended release versions), but whoa, a half-life of several days--that's insanity (literally, at least once you've been awake that long).  But I doubt that any of the indatralines are all that stimulating.


----------



## <pyridinyl_30>

bk = benzyl ketone; C6H5-(C=O)-R

benzyl = C6H5-CH2-R

I bet 2-amino-5,6-dichloroindan is a winner but is probably more of an entactogen than a stimulant.


----------



## Ham-milton

Holy_cow said:
			
		

> ^A compound with similar properties to your pill has been created:N-methylindatraline: Slow-Onset, Long-Duration 3-(3',4'-Dichlorophenyl)-1-indanamine Monoamine Reuptake Blockers as Potential Medications To Treat Cocaine Abuse._ J. Med. Chem. 2000, 43, 4981-4992._ A high dose will last several days. The lasting stimulantion and lack of sleep might not be too good for your mental health.



Except he wanted a releaser, not a reuptake blocker.  For DA, there isn't a major difference of course, the end is both stimulation and euphoria (with some minor differences in subjective feel), but for SE the difference is major.

prozac v. MDMA


----------



## LuxEtVeritas

MDMA is not simply a 5HT releaser, by far


----------



## ebola?

>>I would love to see new stimulant come out that relases serotonin and dopamine like the way meth does
in Depot form tablets that start from 100% relase decreasing each day in 7 days and you'd get no come down at all.
>>

I don't think that the time-release would defeat the crash entirely.  You'd still be in want of sleep, food, dopamine, have too much nor-epi, etc.  As an additional piece of evidence, long-acting stimulants, like meth-amp, can still have nasty crashes.

>>Wouldnt hurt if it relased all serotonin the way mdma does, but kept the high going on for as long as you wanted..>>

This isn't physiologically possible.  The endogenous synth for 5ht is rather slow, so 5ht releasers can deplete (but not entirely) your brain of 5ht within a matter of hours.  This is why meth users can do multi-day binges but ecstacy-users can't really (or when they try, it turns into an expensive stimulant).

ebola


----------



## fastandbulbous

> I would love to see new stimulant come out that relases serotonin and dopamine like the way meth does



It's because methamphetamine acts on both dopamine & serotonin release/reuptake that it exhibits  it's neurotoxicity (amphetamine has very little effect on serotonin and shows only a tiny amount of the neurotoxicity that methamphetamine does) as serotonogic neurones start hoovering up dopamine molecules, whivh because of free radicle oxidation, completely bugger the neurone. On top of that, some drugs that are stimulants with serotonogic activity can cause a really nasty, pretty much untreatable problem for the cardiovascular system, namely pulmonary hypertension; it is related to the 5HT2B receptor. The world can do without a bigger, stronger, faster meth.

A better avenue might be that seen in fencamfamine, which has some activity at the mu receptor (although not enough to cause an opiate sependance). It leads to a smoother stimulant that facilitates concentration (for learning tasks etc) far more than stimulants like amphetamine, meth etc. which quickly lead to repetitive, compulsive behaviour & thought patterns, which do nothing for concentration


----------



## Ham-milton

LuxEtVeritas said:
			
		

> MDMA is not simply a 5HT releaser, by far



Well certainly not, but the comparison is still valid.


----------



## Ham-milton

With stimulants like Dimethocaine, is the tertiary amine necessary?  Perhaps replacing one of the 2-methylpropyl groups with a phenyl would result in opioid affinity.


----------



## LuxEtVeritas

^ that came outtA left field ^  :D


----------



## fastandbulbous

Ham-milton said:
			
		

> With stimulants like Dimethocaine, is the tertiary amine necessary?  Perhaps replacing one of the 2-methylpropyl groups with a phenyl would result in opioid affinity.



How - I can't see how that would get it to fit into the model pharmacophore proposed for mu agonists (where are the 2-methylpropyl group*s* in it's structure?)

structure given here - http://en.wikipedia.org/wiki/Image:Dimethocaine.png


----------



## Ham-milton

I'm sorry, I don't mean one of the two dimethylpropyl groups.  I mean one of the two methyls attached to the propyl.  It made more sense in my head than on paper.  Hope this clarifies.


----------



## elfspice

visualising the likely metabolic breakdown products of desoxypipradrol, got me wondering whether anyone has ever heard anything as such of beta phenyl derivatives of amphetamines. my logic goes, the most likely spot on the molecule it can be attacked is the adjacent carbon to the nitrogen on the piperidine ring, which would produce a lactam, which could then be further oxidised. several people have talked about a secondary effect that occurs somewhere around 4-8 hours after absorption and i was thinking maybe active metabolite?

oh also, i got one hit in this thread on adamantane, a little known stimulant called bromantan which got banned as either a stimulant or a steroid masking agent or both, which is a stimulant with little other than CNS activity, and imunostimulating effects. 

o for a bluelighter living in russia at a university involved in pharmacology research. there's a lot of stuff coming out of russia that you never hear about in the west. http://www.nextbio.com/b/home/home.nb is a site that appears to host summaries of studies of some of these novel russian drugs. http://www.nextbio.com/b/home/home.nb?q=bromantan


----------



## Riemann Zeta

I've always been interested in trying bromantan, but it is extremely difficult to track down.


----------



## elfspice

i found a place willing to synth it but like i said, it's expensive. i also examined the idea of synthesis using adamantane with a keto group and bromophenylamine and still the quote i got came up pretty decent.


----------



## nuke

Substituted anilines don't sound all that appetizing.  para-Bromo aniline is extremely toxic.


----------



## Nagelfar

I'm still thinking the favorable route would be a short acting stimulant, that is a blast of euphoria that is extremely intense/orgasmic and can last as long as you want to redose, to be able to come down whenever you choose, a la freebase coke but needn't be smoked and can be attained by hcl absorption across a membrane, that can be cheaply & easily made for potential of achieving quantity to control length of stimulation more readily.


----------



## nuke

I hate short durations and having to redose, probably because I prefer to dose orally.  4-6 hours is the perfect duration (a la caffeine).


----------



## Riemann Zeta

^I also hate having to redose frequently.  With methylphenidate for ADD, I had to redose 3-4x times per day...sometimes I would completely forget, until the rapid come-down phase started to kick in.  I like a nice 12hr duration, something that works over the course of a day.  I have yet to find anything better than dextroamphetamine XR (especially with respect to the lack of a 'come-down' effect), but I have yet to encounter any desoxypipradrol.  I would love to try that one, but am not expecting miracles, as I tend to respond far better to DAT/NET substrates than DAT/NET inhibitors.


----------



## Nagelfar

I suppose making anything short acting an extended release formulation may be able to help depending on the nature of the absorption? I'd like to think of the 'dream stimulant' as versatile in that it can last a short time if need be. Troparil always sounded good to me, basically coke with no local anesthetic cardiotoxic properties which didn't cause internalization of DAT on the magnitude of the amphetamine & phenethylamine class stimulants and was maybe three times the duration of coke. Anyway, I would think short acting would always equal safer for the most part. I like being able to eat when I want and etc too, that seems to be a large part of the "come down", forgetting when you ate last and neglecting basic bodily functions such as that.


----------



## fastandbulbous

Nagelfar said:


> I'm still thinking the favorable route would be a short acting stimulant, that is a blast of euphoria that is extremely intense/orgasmic and can last as long as you want to redose, to be able to come down whenever you choose, a la freebase coke but needn't be smoked and can be attained by hcl absorption across a membrane, that can be cheaply & easily made for potential of achieving quantity to control length of stimulation more readily.



That is a recipie for disaster as the potential for psychological dependance is so large it would be a nightmare. The last thing you want is a short acvting stimulant. Also the euphoria doesn't last, just like repeatedly administering stimulants - it just leads to compulsive behavior & psychosis


----------



## MrMikecopa

anything that favors dopamine reuptake  and less norepheniphrine stimulation is gonna be a big hit duh! to0much adrenal stiimulation makes u jittery example! caffeine! and  levo amp in adderrall, and benzedrine ect...


----------



## tadfish

Anyone here of DMAA analogs?


----------



## fastandbulbous

Dmaa?


----------



## MokumChemist

DMAA == 1,3-dimethylamylamine or Geranamine.


----------



## Hammilton

I suspect that without closing off the ring and getting propylhexedrine, you can't get better.


----------



## nuke

4-methylpentan-2-amine may be an active analogue.

n-methylgeranamine might be interesting, who knows.


----------



## hamhurricane

quick question, does anyone know if bk-PEA is active?


----------



## hugo24

Well you couldn' t buy then,check out the catalogs on Phenacylamine.


----------



## Hammilton

I don't see any indication that phenacylamine is a stimulant itself, but this patent is interesting: http://www.freepatentsonline.com/4545996.html


----------



## dread

I got this idea for a stimulant/opioid. It resembles fencamfamine, but also fits to the morphine rule. Anyway, it's synthesis should be entirely possible.


----------



## Hammilton

Possible, but I suspect toxicity.

http://pubs.acs.org/doi/abs/10.1021/jo01362a043 <-- probably details synthesis, though I don't have the full.


----------



## Hammilton

Possible, but I suspect toxicity.

http://pubs.acs.org/doi/abs/10.1021/jo01362a043 <-- probably details synthesis, though I don't have the full.

http://www.freepatentsonline.com/3860717.html is potentially useful.

I'd still be careful pursing this, but it seems that the quaternary amine analogues are probably safe enough for administration.


----------



## Jabberwocky

what kind of toxicity do you suspect just out of curiosity?


----------



## dread

Without the methylamine on the side it would just be a mPPP-type opioid. By adding the methylamine it resembles fencamfamine, with the norbornan changed into an azabicyclooctane and methyl instead of ethyl on the amine. 

Ever since I first heard about Lefetamine I have been intrigued by the idea of a drug that would be a stimulant and an opioid agonist at the same time...

But yeah, what about the toxicity? What makes you think so?


----------



## Hammilton

The high likelihood of a MPP+ metabolite isn't enough?


----------



## dread

I don't understand really... how would this metabolize into MPP+?


----------



## Hammilton

MPP+ proper?  Probably not.  An N-methyl derivative, quite possible.  An analogue with the ring opened and then fully saturated (as with MPTP --> MPP+), seems possible.

4-phenylpiperidine derivatives aren't smart to be ingesting, imho.  The 4-phenyl-4- ester piperidine analogues are much safer.  But bingo- they're already DARIs with opioid affinity.


----------



## dread

Well, check out the ring structure of the azabicyclooctane... It's quite different from piperidine when you look it in 3d. It kinda looks like a bird cage. To me it looks like a stable molecule, there shouldn't be too much strain to force it to open...  however this is just a gut feeling. Someone should look into the metabolism of azabicyclooctanes.

Actually, I just did, a bit... I found a drug, azasetron, which contains the same ring structure, azabicyclooctane, and by everything I read the only metabolism that occurs on the azabicyclooctane ring is N-oxidation of the tertiary amine. Nothing I read indicated that the ring structure would open or metabolize into something harmful.

Azasetron:


----------



## Hammilton

a quaternary amine is exactly something dangerous with that motif.  Gets passed the BBB, then is metabolized and can't get back out.

That's exactly what makes dangerous.

It might be totally fine- it's just a matter of whether or not the quaternary amine analogue of that structure would have similar neurotoxic effects.  It's quite possible, and I think you'd be hard pressed to find anyone willing to risk that on themselves.

Considering that rodents aren't a viable research subject, you need primates.  Makes it rather difficult to test this.


----------



## fastandbulbous

Well the structure is actually quinuclidine, which from memory is not subject to any sort of ring opening. Also, I'd imagine most people can think of at least one drug containing a quinuclidinyl structure ie BZ aka 3-quinuclidinyl benzilate


----------



## fastandbulbous

dread said:


> I got this idea for a stimulant/opioid. It resembles fencamfamine, but also fits to the morphine rule. Anyway, it's synthesis should be entirely possible.



Not really as fencamfamine is an alicyclic compound (non-aromatic ring structure) whereas quinuclidine is a heterocycle (ring structure containing a non carbon atom) and as such a lot more different. Also, just because it fits the 'morphine rule' doesn't mean that it's a mu receptor agonist. There is a quinuclidine based stimulant, namely 3-phenyl-2-methylquinuclidine, which is a dopamine reuptake inhibitor (basically in essence a phenmetrazine type of analogue)


----------



## Hammilton

Right, the they share the same azabicyclo[2.2.2]Octane structure.  If N-oxidation (to the quaternary amine) now it's 1-hydroxy-4-phenyl-1-azoniabicyclo[2.2.2]octane which isn't all that different from MPP+ anymore.  Is the aromatic 1-methyl pyridinium structure what makes it neurotoxic or could another quaternary structure be neurotoxic as well?

For some reason I actually hope this hasn't been researched.  Seems like animal cruelty to induce parkinson's in fellow primates.


edit: those 4-phenylquinuclidines are mentioned in one patent as potent analgesics.  Sure, it's possible they're not opioids, but it seems most likely.


----------



## dread

Yeah, I see now that this compound would more likely not be a stimulant.

But I'm still interested in fencamfamine analogues: are there any? 
Actually, tranylcypromine is quite similar, it just has a cyclopropane instead of the norbornane. How about something in the between, like cyclopentane, cyclobutane or cyclohexane? Or does it have to be a bicyclic ring for the stimulant effects?


----------



## Hammilton

Not that I'm aware of, though the cyclohexane is an obvious area of interest!  I'm really amazed it hasn't been seen as an RC yet.


----------



## Holy_cow

Recently I spoke to a Chinese custom synthesis company. I was told that they are working on a large scale-up in the production of 2-DPMP (aka desoxypipradrol). So this shit will probably soon flood the stimulants market. Thank god they don't know certain tricks of the synthesis yet!


----------



## dread

Hammilton said:


> Not that I'm aware of, though the cyclohexane is an obvious area of interest!  I'm really amazed it hasn't been seen as an RC yet.



Yeah, and the synth shouldn't be that hard either. Cyclohexane and cyclopentane should both be interesting, and each of them with either n-methyl or n-ethyl, and all the different diastereomers of them... there's a lot of research to be done here.

edit. Heh, I just realized that the cyclohexane would also be a direct structural analogue of PCE...


----------



## Refluxer

Why would they do a large scale up in synthesis of 2-DPMP? It has it's merits, but is not something the general population wants or should have easy access to. I don't see it becoming very popular, but if it did it'll be a fucking mess. Sleep deprived paranoics wandering the streets. Unless they already received a large order, I'd say it's a miss.


----------



## fastandbulbous

^ Because it is becoming popular 

If it does get turned out en masse though, I know I'm going to end up wishing I'd never opened my mouth about the stuff




> How about something in the between, like cyclopentane, cyclobutane or cyclohexane?



There's already been a clinically used alicyclic stimulant, namely cypenamine (2-phenylcyclopentylamine). The N-alkylated versions might have some decent properties. As can be seen, the bibcyclic structure isn't essential, but having a rigid ring structure must confer some properties otherwise why bother with fencamfamine and just go for 2-phenylcycloheylamine instead as it's much easier to synth

PS Quinuclidine isn't a similar structure to the bicyclic ring structure of fenmcamfamine as quinuclidine has a 2 carbon bridge forming the bicyclic structure whereas fencamfamine has only a single carbon ring spanning bridge


PPS Tranylcypromine isn't the same as fencamfamine (fcf) or cypenamine as the cyclopropyl ring makes the compound a non competetive MAOI whereas cypenamine/fcf are only weak competetive inhibitors. Tranylcypromine puts more people in hospital than any other non-competetive inhibitor and is best left well alone unless hypertensive crises & CVA are your thing


----------



## Refluxer

fastandbulbous said:


> ^ Because it is becoming popular
> 
> If it does get turned out en masse though, I know I'm going to end up wishing I'd never opened my mouth about the stuff



Haha... I would too... even though Shulgin mentioned it, I think your early musings on it made it catch on. Perhaps time to make ADD restricted for viewing in some way?

Either way I don't see it becoming very mainstream. A smaller group of tweakers might like it alot, and some who like the gentle lift of small doses, but I don't think it appeals very much to the general party crowd.


----------



## dread

OK, I drew these just for giggles. Some of these should be good as stimulants. Pick your favorite and start saving for a custom synth... :D


----------



## MurphyClox

Lower row, 1st and 2nd from the left:
You better check geometries of sp2-hybridized carbon again! I'm afraid that ring strain would make those more than difficult to make. The other 2 in the lower row are unsual, too. I'd like to see some suggestions on economically feasible synthesis of those...if such discussion would be allowed here. So, rhetorical comment. 
But generally spoken, I don't think that these are valuable targets.

The first row...ummm...okay but IIRC will the steric demand in the beta-position decrease activity.

- _Murphy_


----------



## Hammilton

no, and a double bond doesn't apparently offer anything, either.


----------



## dread

Hmm, I'm not sure why I made it a double bond. Maybe I was uncosciously thinking of etorphine...


----------



## ResinTeeth

I'd like to see a stimulant whose effects resemble cocaine's but being much longer acting


----------



## fastandbulbous

^ How much longer? There are cocaine derived DARIs that are reckoned to act for a couple of days.

Probably something like amfonelic acid would fill the gap you're hoping to fill as long as you don't want the local anaesthetic action (which is where a lot of cocaine's toxicity resides)


----------



## Hammilton

if only it were cheap enough for the RC market to put out...  At least this means it should stay legal.


----------



## MurphyClox

MurphyClox said:


> Lower row, 1st and 2nd from the left:
> You better check geometries of sp2-hybridized carbon again! I'm afraid that ring strain would make those more than difficult to make.


I revoke this particular statement! Was some kinda confused but it is obviously possible to build such ring-systems. Sorry!


----------



## dread

> it is obviously possible to build such ring-systems.



Yayy


----------



## tadfish

Whats everyone think about the 4-fluro range of RC's like 4flurococaine and 4-fluor-methamp that seems to be getting added to everything does that make it legal or what. sorry for sounded dumb i am dumb right now.
and what health risk does the 4-fluro add or is it a more safer version. I wonder alot aobut this 4flurococaine 60 times more stronger sounds like a heart attack in one ay. from what i heard 4fluro drugs are bad for heart and coke is toxic as for heart destroying tissue on contact of the heart.


----------



## Hammilton

With (dopaminergic)stimulants 3,4-dihalo increases potency; 3,4-dichloro is generally the most potent substitutent.  Para-fluoro generally results in a more serotonergic nature for the simpler PEA derived stimulants.

With the tropane stimulants, I wouldn't worry so much about increased toxicity, it should actually be much less.  Because it's not something that increases local anaesthetic activity, you're actually reducing the damage on the heart vs. cocaine.

However, with the PEA derived stimulants para-halo is *generally* something that increases toxicity.  para-fluoro is the safest of these, by far, and doesn't display the toxic effects that things like para-chloro-phenylalanine or para-chloro-amphetamine does.


----------



## immad

What do you guys think about Bromantane? It seems to me that a stimulant that mainly targets dopamine and serotonin should be really smooth, without noradrenaline, while the serotonin is calming, like meth vs amph. Or am I terribly wrong here?


----------



## Hammilton

Probably.  Compare it to cocaine minimized in 3D


----------



## tadfish

Whats everyone think about the 4-fluro range of RC's like 4flurococaine and 4-fluor-methamp that seems to be getting added to everything does that make it legal or what. sorry for sounded dumb i am dumb right now.
and what health risk does the 4-fluro add or is it a more safer version. I wonder alot aobut this 4flurococaine 60 times more stronger sounds like a heart attack in one ay. from what i heard 4fluro drugs are bad for heart and coke is toxic as for heart destroying tissue on contact of the heart.


----------



## vecktor

tadfish said:


> Whats everyone think about the 4-fluro range of RC's like 4flurococaine and 4-fluor-methamp that seems to be getting added to everything does that make it legal or what. sorry for sounded dumb i am dumb right now.
> and what health risk does the 4-fluro add or is it a more safer version. I wonder alot aobut this 4flurococaine 60 times more stronger sounds like a heart attack in one ay. from what i heard 4fluro drugs are bad for heart and coke is toxic as for heart destroying tissue on contact of the heart.


^
perhaps they cause short term memory loss, focus difficulties, repetitive behaviours, as evidenced by repeat posting and failure to read the posted replies. 




people should be aware that fluoromethamphetamine is not legal, and has only a narrow dose window, from mediocre effects at lower doses to downright unpleasant effects at 20-30% above. the material shows clear acute toxic effects. the n demethylated amphetamine *appears* less toxic than the methamphetamine, but this is all terra incognita. 

4-fluorococaine (4'-flourobenzoyl ecgonine methyl ester) is not 60x more potent than cocaine,  the related CFT is, but it is not around as it is very expensive and is synthesised from illegal cocaine, both CFT and 4-fluorococaine are illegal in quite a few countries.

it is 4-fluoro *tropa*cocaine that has appeared in quantity this is 4-fluorococaine without the ester group, and seems quite effective in a compulsive coke kind of way, it is cheap and available.


----------



## psynirvana01

who keeps deleting my posts?... seriously whats your deal man? you should be a cop or some other authoritative figure.


----------



## immad

A few weeks ago I had approx. 100 mg of 4-fluoro-tropocaine, which seemed to sedate me to some extend. Like, I got the urge to lay down and/or fall asleep. I've heard others had this too off this batch, could this be a botched synth or is it indeed less up than coke? In a way, it did feel like coke though.


----------



## nuke

My thoughts are still with the 3,4-di or mono fluorinated methylphenidates or the ethylphenidate/propylphenidate or some mixture thereof.  They should exert very high affinities for DAT.

I wonder about 5-phenyl-1,3-oxazol-2,4(5H)-dione (pemoline with the imine replaced by a ketone).


----------



## Riemann Zeta

Mmm, something about that bariturate-like aminomalonate-esque moiety in 5-phenyl-1,3-oxazol-2,4(5H)-dione isn't sitting well with me.  It's screaming hepatotoxicity...possibly even CNS depressant.


----------



## Hammilton

I'd be worried it'd be a GABA antagonist; all of these that are depressants are substituted IIRC.  It's most similar to phenytoin, I suppose, but that's two phenyl groups like diphenylprolinol.

Obviously without similar activity though!

Is the monophenyl derivative of phenytoin known?

Hmm..  I'd be wary:



> Xenobiotica. 1989 Dec;19(12):1471-81.
> Related Articles, Links
> 
> Teratogenicity of phenylhydantoins in an in vitro system: molecular orbital-generated quantitative structure-toxicity relationships.
> 
> Brown LP, Lewis DF, Flint OP, Orton TC, Gibson GG.
> 
> University of Surrey, Department of Biochemistry, U.K.
> 
> 1. The ability of 20 mono- and di-phenylhydantoin derivatives to inhibit differentiation of rat embryo mid-brain and limb bud cells in culture has been used as an index of the teratogenic hazard represented by these compounds. 2. Molecular orbital calculations on these compounds, using the MINDO-3 (modified intermediate neglect of differential overlap) and CNDO-2 (complete neglect of differential overlap) methods, were combined with indices of teratogenicity in the two cell types, to generate a coherent structure-toxicity relationship. 3. Teratogenicity correlated with frontier orbital electron density of the N1 hydantoin ring atom (HOMO-N1) in a sub-series of 12 monophenylhydantoins, whereas the corresponding toxicity for both mono- and di-phenylhydantoins related more to the molecular polarizability (alpha mol) of the molecule. 4. Furthermore the same structural parameter (alpha mol) exhibited a parallelism with log P values of these 20 compounds, indicating the importance of lipophilicity in the toxicity of these compounds. 5. Overall, the data emphasize the ability of electronic structural calculations to identify chemical descriptors of toxicity.


----------



## Riemann Zeta

I was also thinking phenytoin, which, like the barbiturates, is one of those chemicals that does some crazy shit to the liver.

Edit: and can cause flipper babies.


----------



## nuke

Pemoline wasn't exactly kind to the liver to begin with.


----------



## Riemann Zeta

^^ Isn't that why it was shitcanned?  Several people experienced severe hepatic toxicity, with a couple of deaths from acute massive liver failure.


----------



## nuke

In children mostly.  Some people took it for 10+ years and never saw a problem.

Someone else decided to use aminomethylation to make various active/prodrug forms of the compound.  Never heard anything about their development, though.  I think it may be the cyclic imine causing the problems but I'm not completely sure.


----------



## nuke

United States Patent Application 20040014992 has some neat compounds which are DAT inhibitors too -- non-nitrogenated ones at that.


----------



## Hammilton

Isn't this 3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methoxyphenyl)propan-1-one o-1793 or 94?  I'm not sure which.  It reminds me of the dimethocaine type stimulant.

Then O-1783 is one of these 8-thiabicyclo[3.2.1]oct-2-enes or "thiatropanes"?  There were cocaine analogues with the nitrogen replaced by a carbon that was also quite potent.  Hmm..  it says that the 3,4-dichloro thiatropane analogue is a potent and selective SSRI, 800x higher affinity for the serotonin transporter than DAT?


----------



## Hyperspace

So far, no one in here has yet to bring up the idea of selenium containing stimulants.  Which is interesting, since there's already an active psychedelic containing selenium.  The most likely candidate for a stimulant containing selenium would be 4-methylseleneoamphetamine.  An analogue of 4-MTA with a selenium in place of the sulfur.  I can't find any info on this compound, so it probably hasn't shown up in any articles.

As for the potency of this compound, it's hard to say here.  I don't think it will be more potent than 4-MTA and will probably induce serotonin syndrome like PMA and 4-MTA do, which means it'll have some of the dangers of those two compounds.  I doubt it will have psychedelic activity either (which PMA does have).


----------



## LuxEtVeritas

maybe i am just drawing a blank and have seen it but to my recall i cannot think of any selenium containing psychedelics,...please enlighten


----------



## vecktor

LuxEtVeritas said:


> maybe i am just drawing a blank and have seen it but to my recall i cannot think of any selenium containing psychedelics,...please enlighten



there is 2-C SE or whatever Shulgin called it in Pihkal which was mildly interesting.

selenium compounds generally are bad smelling, toxic and on the whole horrible.


----------



## nuke

Nepicastat - A dopamine beta-hydroxylase inhibitor intended to treat cocaine dependence.  It may actually be sedating due to the negative effect on norepinephrine concentrations.

http://en.wikipedia.org/wiki/Nepicastat



> Isn't this 3-(1H-1,2,3-Benzotriazol-1-yl)-1-(4-methoxyphenyl)propan-1-one o-1793 or 94? I'm not sure which. It reminds me of the dimethocaine type stimulant.
> 
> Then O-1783 is one of these 8-thiabicyclo[3.2.1]oct-2-enes or "thiatropanes"? There were cocaine analogues with the nitrogen replaced by a carbon that was also quite potent. Hmm.. it says that the 3,4-dichloro thiatropane analogue is a potent and selective SSRI, 800x higher affinity for the serotonin transporter than DAT?


I'm not terribly sure.  I went through the patent again but the wording escapes me.


----------



## LuxEtVeritas

vecktor said:


> there is 2-C SE or whatever Shulgin called it in Pihkal which was mildly interesting.
> 
> selenium compounds generally are bad smelling, toxic and on the whole horrible.



indeed it could be attached to anything but part of the criteria at least to me to call it such would be that it is at all truly worthwhile and indeed either superior to its non-selenium counterparts in some way as otherwise it is a dead end to the assumed goal of superior compounds and movements off SAR


----------



## LuxEtVeritas

nuke said:


> Nepicastat - A dopamine beta-hydroxylase inhibitor intended to treat cocaine dependence.  It may actually be sedating due to the negative effect on norepinephrine concentrations.
> 
> http://en.wikipedia.org/wiki/Nepicastat
> 
> 
> I'm not terribly sure.  I went through the patent again but the wording escapes me.



i would think a DA beta-hydroxylase inhibitor would make the use of such compounds MORE pleasuable and thus how would it treat dependency...?

Such is a great compound area to improve compounds that have too pronounced NE and allow one to get more of the DA with less perhaps as well


----------



## Riemann Zeta

I wouldn't count noradrenaline out of the equation to produce a good stimulant compound.  As long as the compound is lipophilic enough to primarily accumulate in the brain, NET substrates can release central noradrenaline, as well as dopamine in the frontal cortex via the NET (there are more NETs than DATs presynaptically in the prefrontral cortex, so some dopamine gets sucked up by adrenergic neurons).  Since amphetamine (both _d_-amph and _dl_-amph) has equivalent affinity/efficacy at both the DAT and the NET, it has some decent cognition enhancing effects.  _d_-Methamphetamine does have a greater affinity for dopamine transporters and while it is a more potent stimulant, it is also more hedonic (hence, addictive) with a weaker pro-cognitive effect and is significantly more toxic than amphetamine itself.  Noradrenaline can be a good thing, as long as it's not peripherally creepy-crawly and all annoyingly hot and bothered--of course, some dopaminergic activity is essential, otherwise the whole thing just gets disgusting, like (-)-ephedrine, phentermine or atomoxetine.


----------



## Rectify

Forgive me, if necessary, for not having just read this entire 35 page thread, but in the spirit of "not counting noradrenaline out," what about the six 
(3,4-MD)-(50:50 R/S)-beta-methoxy(meth,eth)amphetamines?

2C-beta-MeO-MDA is active, according to PiHKAL (in which it has its own entry), and none of the above 6 compounds would be particularly hard to make, especially (R, S, or 50:50 R/S)-beta-MeO-methamphetamine.


----------



## Nibiru

What about the possibility of indolic stimulants? I mean, indolic compounds have shown a wide range of biological effects, and yohimbine is an indole and a fairly powerful stimulant. Although a fair amount of indolic compounds are psychedelic, you have things like the harmal alkaloids and ibogaine, which do wierd things fairly different from the more typical indolic psychedelics. And you also have stuff like AMT, which has an almost MDMA like effect (the closest thing I've come by to it in several regards) albeit a very psychedelic one.

Is the likelihood of powerful indolic stimulants possible in the same way that phenethylamines can run the gamut from balls-trippy psychedelic compounds, thru sort of semi-psychedelic euphoriants like MDA, to very plainly stimulating ones, or is the fact that there are relatively few if any straight up indolic stimulants with amphetamine-like effects indicative of the unlikeliness of it being possible? Could anyone with a better knowledge of neuropharmacology and organic chemistry than I have enlighten me? I'm sure this territory has  to have been charted a little bit at least.


----------



## Rectify

Indoles are wicked.  Just look at all the recent problems with JWH-018, for example.

Yeah, I know that there's got to be a Yin for every Yang and all that, but Lord, take a whiff.


----------



## astrang123

I am far from a chemist myself, so I cant comment on chemically altering stimulants to make more effective/euphoric. Just throught it would be useful to mention here that I did read up that a new drug is being passed by the FDA in the US, which is a transdermal extended release patch of the drug, mehtylphenidate. Supposedly this new patch will last 9 hours and will provide superior drug deliverence of the ritalin (methylphenidate) into the system. That should be interesting to see where it is scheduled and what the abuse potential of the new transdermal system is.


----------



## immad

^Most of the time, addictiveness is (party) determined by steepness of the concentration of the drug in the brain, aka the "rush". (That's a big reason why people IV their stuff).

Transdermal is a pretty slow delivery mechanism afaik, so I guess it doesn't promote addictiveness / abuse potential.


----------



## LuxEtVeritas

^ correct, unless load is really high, such as if you use a whole bunch of patches at once...it can be abused, but has somewhat less potential

if you cover yourself in patches though, well...

i assume for now it is considered as the same sched regardless of format

gotta love Xyrem is a CIII and GHB is a CI and CI designates there is NO medicinal use whatsoever

they can;t even keep blatant hypocrisy out of their legislation...pathetic...


----------



## MobiusDick

BilZ0r said:


> Stimulants I think are one thing that people could hold out some hope for a new, plant derived drug. The monoamine transporters are so promiscuous, it seems all you need is a benzene and a nitrogen somewhere... and your in.



I think that classes of stimulants basically discovered so far are those that affect DA and NE (the amphetamine type) and DA, NE and 5HT (the cocaine type). But further differentiation may come into play with those that affect the DAT vs those that affect the VMAT-2, and they may already be available.

The other possibility will (IMHO) be stimulants that affect orexin (modafinil being one of the first of its type, with a very weak orexin interaction.) 

I am convinced that aminorex and 4-methyl-aminorex work through some alternative method, although my evidence is anecdotal.

MobiusDick


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## LuxEtVeritas

^ you are forgetting GABA antagonists, amongst other paths that have a stimulant effect


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## Hammilton

> I am convinced that aminorex and 4-methyl-aminorex work through some alternative method, although my evidence is anecdotal.



If by 'work through' you mean they have some other minor interaction: possibly.  We have numbers showing that they're potent DARIs though.  Or were they primarily releasers?  oh well.


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## LuxEtVeritas

Hammilton said:


> If by 'work through' you mean they have some other minor interaction: possibly.  We have numbers showing that they're potent DARIs though.  Or were they primarily releasers?  oh well.



indeed they are notably dopaminergic in their mode of action


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## hugo24

5-(2-Aminopropyl)-indole (the "5" AMT analog) is an active, long lasting stimulant at 20mg,per THIKAL,you can read it up under AMT there,the other isomers are also discussed as is the "Phentermine" analog.




Nibiru said:


> What about the possibility of indolic stimulants? I mean, indolic compounds have shown a wide range of biological effects, and yohimbine is an indole and a fairly powerful stimulant. Although a fair amount of indolic compounds are psychedelic, you have things like the harmal alkaloids and ibogaine, which do wierd things fairly different from the more typical indolic psychedelics. And you also have stuff like AMT, which has an almost MDMA like effect (the closest thing I've come by to it in several regards) albeit a very psychedelic one.
> 
> Is the likelihood of powerful indolic stimulants possible in the same way that phenethylamines can run the gamut from balls-trippy psychedelic compounds, thru sort of semi-psychedelic euphoriants like MDA, to very plainly stimulating ones, or is the fact that there are relatively few if any straight up indolic stimulants with amphetamine-like effects indicative of the unlikeliness of it being possible? Could anyone with a better knowledge of neuropharmacology and organic chemistry than I have enlighten me? I'm sure this territory has  to have been charted a little bit at least.


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## Riemann Zeta

^^ I really like the look of this molecule.  It is an interesting variation on the traditional 3,4-substituted amphetamines.  I vaguely recall discussing it on bluelight years and years ago, thinking that it might be a good non-neurotoxic MDA analogue, lacking the problem of conversion to pro-oxidant metabolites via the 3,4-dihydroxyamphetamine intermediate.

The only conceivable problem with it might be activity the 5-HT2B receptor...which could only be revealed by an in vitro receptor binding/efficacy study.


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## nuke

Ring aminated phenethylamine like stimulants tend to be even more toxic...  if metabolism breaks the ring open you'll end up with an aniline.


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## Hammilton

Not an indole, but somewhat related is mazindol with it's impressive NE reuptake inhibition.


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## Holy_cow

Hammilton said:


> Not an indole, but somewhat related is mazindol with it's impressive NE reuptake inhibition.


Mazindol is not "rewarding" or pleasant at all, though, but rather causing dysphoria.


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## dread

nuke said:


> Ring aminated phenethylamine like stimulants tend to be even more toxic...  if metabolism breaks the ring open you'll end up with an aniline.



Well if the indole ring could be broken up by metabolism, wouldn't that also make all the tryptamines toxic?

Anyway, what about the benzofuran and benzothiophene analogues of this chemical...


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## Nibiru

Mazindol is just plain strange.

It's not rewarding, but it definitely has sympathomimetic properties, making it pretty much a stimulant. Modafanil isn't very rewarding either, and neither is yohimbine, arguably, but they are definitely stimulating.


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## LuxEtVeritas

i would consider all those stimulants as that is a primary effect even if overall they are not classical in nature

few, but some, i believe can get a nice effect off Maz...nothing stunning, but as with Yohimbine it is very user specific as to a good, bad, or ugly effect

obviously modafinil is a stimulant and rarely has any negative effects, though indeed it is not usually recreational for anyone, but can aid functional capacity greatly


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## Riemann Zeta

Mazindol is definitely a stimulant--it will keep you awake.  It is somewhat interesting in the fact that it is rather translucent: it doesn't feel good, but it also doesn't feel particularly bad.  Yohimbine, on the other hand, is simply disgustipating in every way.


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## dread

Hmm... I wonder if 3,4,n-trimethylamphetamine would be stimulating...


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## tadfish

4fluorococaine so whats it like? 
effects duration strength etc.
is 4-fluro cocaine the same as 4-fluoro-tropocaine?
100mg seems like alot how did u have the dose, orally, snort, IV....etc???


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## tadfish

immad said:


> A few weeks ago I had approx. 100 mg of 4-fluoro-tropocaine, which seemed to sedate me to some extend. Like, I got the urge to lay down and/or fall asleep. I've heard others had this too off this batch, could this be a botched synth or is it indeed less up than coke? In a way, it did feel like coke though.


how did u have it


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## nuke

dread said:


> Well if the indole ring could be broken up by metabolism, wouldn't that also make all the tryptamines toxic?
> 
> Anyway, what about the benzofuran and benzothiophene analogues of this chemical...



There's quite a lot of steric hindrance on the one position in tryptamines as compared to that stimulant.  Even if it didn't open, there could be substantial neurotoxicity associated with it anyway.

Two benzofuranyl analogues have been prepared by Shulgin and are published in PiHKAL.  The activity was not established but they did not appear to be potent.


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## PetersKeys

joystick said:


> I have a prescription for phenDImetrazine (phenmetrazine with an extra N-methyl group).  Phendimetrazine is metabolized by the body, according to my Physician's Desk Reference, to phenmetrazine and phenmetrazine N-oxide.  While I enjoy my monthly phendimetrazine fix, it does not compare to methamphetamine.  Neither does Ritalin (methylphenidate) or Adderall (amphetamine).
> 
> I think clear, recrystallized, nearly pure dl-methamphetamine hydrochloride is probably going to remain king of the stimulants for some time.  Its synthesis is easy, it is chemically synthesized from a naturally occurring alkaloid derived from the Chinese ma huang plant, the quality of its high is very good, and the high lasts a long time.  However, I would like to try the heretofore unscheduled 2-benzylpiperidine, a methylphenidate analogue designed to have a much longer half life than methylphenidate, as a possible stimulant.
> 
> Cocaine doesn't last long enough for me, is too expensive, and has agonizing come downs.  Plus, the first thing many people do after doing some cocaine is have to take a nasty shit while they are high.  Sure, some cocaine analogues may be very powerful, but they will always be extremely expensive to synthesize as long as they rely on cocaine as their starting material. As for the entactogens, I don't think MDMA / MDA can be beaten either, even though I am on methylone (that is, MDMCAT) right now.  OTOH, I would like to try 3,4-dichloromethamphetamine.
> 
> Caffeine and nicotine, two legal stimulants, will probably also continue to be used extensively in the future.  Speaking of nicotinic agonists, I would also like to try ABT-594.
> 
> Modafinil and ephedrine are crap drugs in my opinion.






I agree somewhat. I think methamphetamine is gonna remain king for a long time. The only thing that I think could make it stronger would be something like an extra methyl group attached that would make it absorb even faster through the BBB. 

Rather than the pharmacological strength of the drug I think it would be better to focus more on the drugs Dopamergic release, flooding, affinity, and re-uptake effects. There are many powerful stimulants with shitty euphoria and pleasurableness. All stimulant addicts pretty much want is an enormous surge in dopamine for their high. Amphetamine itself has a very similar structure to dopamine

Cocaine anologues probably won't make it on the black market due to their expensive production costs. But I definately see a future for newer anti-depressants from cocaine analgues like Tesofensine and Brasofensine


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## Hammilton

You have no idea what you're talking about.  N,N-Dimethylamphetamine is fairly weak.

N,a,a-trimethylamphetamine is also fairly weak.  None of the a,a-dimethylamps are interesting.

Cocaine analogues have already appeared on the blackmarket, so that's just another dumb comment.  People are willing to pay for anything that they might perceive as 'less illegal.'


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## PetersKeys

Nibiru said:


> Mazindol is just plain strange.
> 
> It's not rewarding, but it definitely has sympathomimetic properties, making it pretty much a stimulant. Modafanil isn't very rewarding either, and neither is yohimbine, arguably, but they are definitely stimulating.



yohimbine is horrid in my opinion. All the nasty side effect of a harsh stimulant with none of the good effects. Worst experience ever.


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## Rectify

I didn't get great results with it either.


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## MurphyClox

Hammilton said:


> You have no idea what you're talking about.  N,N-Dimethylamphetamine is fairly weak.



Correct (ca. one tenth the potency of methamphetamine, IIRC), but one must not forget that in contrary to meth there was no significant neurotoxicity shown for N,N-dimethylamphetamine, which is a quite inviting property. I think that deserves some consideration.

Ref: _Brain Res_ *1997*, 771, p.115
(thx to LuxEtVeritas)

Peace! _Murphy_


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## Hammilton

Yeah, but is that just because it's slower in producing DA efflux?  ANd thus less enjoyable?


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## Lupus

MurphyClox said:


> Correct (ca. one tenth the potency of methamphetamine, IIRC), but one must not forget that in contrary to meth there was no significant neurotoxicity shown for N,N-dimethylamphetamine, which is a quite inviting property. I think that deserves some consideration.
> _Murphy_



When was it concluded that methamphetamine is toxic in oral doses? Aside from one of ricaurte's studies anyway.


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## Hammilton

Why don't you do some reading.  That's a really really really easy to answer question if you look yourself.


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## Hammilton

Why don't you do some reading.  That's a really really really easy to answer question if you look yourself.


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## Lupus

Hammilton said:


> Why don't you do some reading.  That's a really really really easy to answer question if you look yourself.



I have, thats why im curious as to what he's talking about. The only definitive research i've read that can directly correlate neurotoxicity to meth use was one involving IV users.  The fast onset was what was determined to be the factor in doing damage to DAT receptors. 

The only other thing that i can think of is the increased levels of glutamate simply causing cells to burn out..

This is of course excluding any of ricaurte's research.


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## vecktor

Lupus said:


> I have, thats why im curious as to what he's talking about. The only definitive research i've read that can directly correlate neurotoxicity to meth use was one involving IV users.  The fast onset was what was determined to be the factor in doing damage to DAT receptors.
> 
> The only other thing that i can think of is the increased levels of glutamate simply causing cells to burn out..
> 
> This is of course excluding any of ricaurte's research.



People are making a monementally dumb mistake by discounting Ricaurte, he admitted a mistake was made in accidentally substituting METH for MDMAin one set of experiments, which indicated erroneously that MDMA was a dopaminergic neurotoxin. 

HE highlighted the error and published a retraction/correction, that shows that he actually does care about science and the accuracy of what is published. 
This is in contrast to rather a lot of the other reserch out there that is plain wrong,  plagarised or downright fraud, where the authors know there are issues but don't publish corrections.
I don't discount his work, but I am careful to check it properly and not rely on it as a sole source of data, becuase there is the possibility of sloppy lab work.

I can name others whose research is much more dubious, some are blatent.


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## MurphyClox

Searching for "methamphetamine neurotoxicity" in SciFinder yields not less than 260 hits. I think there's no doubt about that.

- _Murphy_


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## dread

Lately I've been wondering, if n-methylating alfetamine would give it more stimulating qualities...


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## Hammilton

I kind of doubt it, but it doesn't seem to be very well researched.

I'd be more interested in knowing about alpha-allyl versions of things like MDPV and the cathinones.


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## dread

> I'd be more interested in knowing about alpha-allyl versions of things like MDPV and the cathinones.



Funny, I've been thinking exactly the same.  

Then I've been thinking you could replace the pyrrolidine with a morpholine... 

Also you could bend the alkyl-chain of MDPV back to the phenyl to make it into an indane (or indanone, with the b-ketone)...


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## c0rt3x

I had a few ideas about - as far as I know - new stimulants







*1,1-diphenylpropan-2-amine* -> Amphetamine meets Desoxypipradrol...






*methyl(2-phenylethyl)amine* -> PEA meets Methamphetamine






*1-benzoyl-4-methylpiperazine* -> MBZP meets Cathinone


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## btrswiet7u4ia

:D Caffeine. My drug of choice. Hands down.


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## Hammilton

I would expect shitty shitty shitty activity from 1-benzoyl-4-MePiperazine.


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## c0rt3x

@Hammilton:

Could you please explain why you think 1-benzoyl-4-methylpiperazine wasn't a good idea?

And what do you think abou the other two?


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## shith3ad

guess u couldnt appreciate the humor in the last one huh......

ok it doesnt have to be donuts then.....lol


:http://www.cognitiveliberty.org/shulgin/adsarchive/acacia.htm


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## dread

3-(Methylenedioxyphenyl)-morpholine, how about it?

And how about: 2-phenyl-3-ethylamino-tetrahydrofuran? (or methylamino, why not..)

And: 1-benzyl-1-ethylamino-cyclohexane? 

Or ... b-keto-n-methyl-alpha-isopropyl-phenethylamine?

Or this: 5-methoxy-2-morpholin-4-yl-indan-1-one?

Sorry, cba to draw/upload pics. Mayhaps later.


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## vecktor

this thread is now far too large.

to continue discussion  please start a new thread called stimulants of the future II


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