1-{1-(3-Methoxiphenyl)-cyclohexyl}-piperidin

[hugo24]

I think I have read up all availble information on 3-MeO-PCP (and 3-HO-PCP),but I couldn't find any reliable human data on it.Some have speculated a batch sold as PCP was in fact the 3-HO,leading to tension and headaches,but IF the activity of the phenol is indeed 8x higher its a bit hard to believe (unless it was diluted).

Qualitywise are the effects allegedly quite similiar to PCP (and the same plus in regards to metabolic degradation as its 4-MeO cousin).

And its proposed mu activity is proably still too low for these doses as C6H6 claimed.

The DRI potency of these two analogs is anybodys guess,I must say though I would prefer a serotonergic window.The 3-Methoxi adds some erotic to the compound (if chemical structures can turn you on %) ). Tramadol isn't too far off either.

Any new info about the two compounds would be appreciated.

 

[Rectify]

I don't know the answer to your question exactly, but based on my past knowledge and experience, I have a hunch that
1-ethylamino-1-(2-methylphenyl)cyclohexane (with the ethylamine switched with piperidine if potency is what you're after) is going to turn out to be more of a winner in the end than any of the MeO-PCPs.

Why?

Because (1) I thought PCE was lovely and (2) it's a sort of a cross between ketamine and methaqualone structurally and (3) I don't think these drugs are acting on the dopamine/adrenaline/noradrenaline receptors directly like the amphetamines do and thus don't need any phenoxys at all to carry out their art of mimickry any better.

Plus, (1) we know that the metabolism of PCP goes something like the following:

PCP --> 4-OH-PCP --> 4-MeO-PCP

And (2) drugs generally get progessively weaker as they are metabolized by the human body, with (possibly) the exception of
3,5-dimethoxy-4-methylphenethylamine [which may or may not even be active] and the like, so it would make sense that 4-MeO-PCP is 10x weaker than PCP based on this analysis.

 

[Hammilton]

Because (1) I thought PCE was lovely and (2) it's a sort of a cross between ketamine and methaqualone structurally and (3) I don't think these drugs are acting on the dopamine/adrenaline/noradrenaline receptors directly like the amphetamines do and thus don't need any phenoxys at all to carry out their art of mimickry any better.

(2) The compound you suggest bears little similarity to ketamine- if that counts as similar to ketamine, then any PCP derivative an N-alkyl group is going to. Similar to PCE, but not ketamine. The comparison to methqualone is laughable. Why, because it has an ortho-methyl? Well I guess it's also related to orphenadrine, tolvaptan, metolazone, prilocaine and dapiprazole are also all related to this. That's really scary news because it's going to be a muscle relaxant, a competitive arginine vasopressin receptor 2 antagonist, a diuretic, a local aneasthetic, and an alpha blocker. Thank god it bears as little similarity to these as it does to methaqualone.

(3) What? PCP is a rather strong DARI, ketamine isn't as strong, but PCE and these derivatives will as well. IIRC, BTCP is one of the strongest DARIs known.

 

[Rectify]

Why? Because it has an ortho-methyl phenyl group?

Yes, actually. That was all that I was saying.

As for the ketamine analogy, simply Ar-Cl --> Ar-Me. I don't see the need to make fun of my hypothesis. It's a conjecture, admittedly, loosely based on my intuition and flights of fancy and personal experiences and whatnot. But I also found orphenadrine to be quite hypnotic and trippy as well, now that you mention it, which only buttresses my assertion in my mind's eye.

"But logic? Logic has nothing to do with any of it [drug design]."--from Phenethylamines I Have Known and Loved: A Chemical Love Story.

 

[Hammilton]

As for the ketamine analogy, simply Ar-Cl --> Ar-Me.

And the n-alkyl is one carbon longer, and the cyclohexyl is unsubstituted where ketamine has a 1-oxo group.

I don't see the need to make fun of my hypothesis. It's a conjecture, admittedly, loosely based on my intuition and flights of fancy and personal experiences and whatnot. But I also found orphenadrine to be quite hypnotic and trippy as well, now that you mention it, which only buttresses my assertion in my mind's eye.

You're making SAR predictions based upon drugs that don't even act on the same receptors. If you find that orphenadrine's effects reinforce your ideas about 1-methyl-eticyclidine, you're insane. Or intoxicated. I don't care which, either seems equally likely. I'd suggest reading anything you can about SAR studies so you can have even a remote understanding of what you're saying.

Your Shulgin quote is irrelevant. Logic didn't have anything to do with his work- he was starting on largely virgin soil and so had no SAR studies to go from- and instead was essentially building his own. That's not the case here.

There may be reasons for the ideas you're suggesting, but none of reasons you've suggested thusfar even come close to the mark.

I'm sure 4-(methylamino)-4-o-tolylcyclohexanone has been prepared and compared with ketamine, but I'm fairly certain that ketamine loses it's mu opioid receptor affinity when the chloro is removed. Deschloroketamine was investigated as an antibacterial agent.

 

[vecktor]

SAR is dead long live SAR:
http://pubs.acs.org/doi/abs/10.1021/ci700332k

one of a large number of papers pointing out the intrinsic problems of extrapolating data and correlating factors.

 

[Rectify]

Thank you, vecktor. SAR is indeed dead. In fact, it was never living.

Hammilton,

Feel free to refrain from repeated personal attacks. You're not the only smart person in the world, and yours is not the only valid way of thinking.

 

[Hammilton]

SAR is dead long live SAR:
http://pubs.acs.org/doi/abs/10.1021/ci700332k

one of a large number of papers pointing out the intrinsic problems of extrapolating data and correlating factors.

More than a little apple and orange, don't you think?

There's a world of difference between what is attempted with QSAR and making a predicting based upon a large number of closely related structures.

There's a whole world of difference between idiotic comparisons between unrelated structures containing minor structural similarities (especially when there are hundreds of other structures containing the same features for which there is no remotely related activity) and making predictions based upon closely related structures where the same modification repeatedly produces similar results.

It's little stretch to suggest that an active dose of dextro-Xorphanol will have effects similar to DXM and the other dextro isomers of these opioids.

Feel free to refrain from repeated personal attacks. You're not the only smart person in the world, and yours is not the only valid way of thinking.

You suggest that because orphenadrine had 'trippy' effects is relevant to the compound you suggest? I may not be the only, but statements like that confirm my suspicions that there are fewer smart people around than I originally though.

 

[wungchow]

Hammilton, quit acting like a little bitch. I bet you would be really irritating to hang out with in real life.

 

[hugo24]

Can this 1-{1-(3-Methoxiphenyl)-cyclohexyl}-piperidin be inactive? I have 5mg on board and I feel not much to be honest! If at all,it feels more like a weak opiate buzz which it isn't supposed to be according to the textbooks.Strange.

 

[Hammilton]

Wasn't the 4-Methoxy derivative active around 30mg? Have to google around, but I'd suspect that the dose is just too low.

 

[hugo24]

Okay I take back the inactive part,it has been quite an effective dose!!Its just not what I expected.

I still feel the brain fog today (the day after) like from a good dose of a typical dissociative.Altough the fog is more like a very relaxed and lazy state.But what the hell does this compound do? I see that it could be addictive in certain individuals,I was in a state I've not been before!I have to clear this fog up first before going into details.

I've read that about the 4-Methoxi Hammilton,but binding data from the meta analogs asked for starting very low.

 

[hugo24]

I tried this first on Wednesday at 400ug,with almost no effect,maybe some relaxation,probably a placebo effect.

On Saturday I increased the dose to 1mg (slightly sweet taste) ,after an hour passed by I took 2mg more as there apeared still no truly detectable effect.Another 30' later,the next 2mg went in for a total of 5mg.Half an hour passed by again until I sensed a true onset of something.While the typical dissociatives "sand" like numbing of mouth and lips were present,the psychological state was one of well being with a slight opiatelike buzz.

It got stronger then, altough the analgetic effect was not comparable to PCP,even some tactile enhancement noted.There was a surprising strong eroticism,I watched TV and got turned on by the look of female faces.

About 3h after the first dose the peak was achieved,I felt quite drugged with a headache but it was in no way that disabilitating as other dissociatives at "comparable" levels even though it never felt like a low dose.Walking went fine as did doing tasks.But I had no drive to do anything,just laying there.I always felt good,in fact way better than usual,no manic excitement,just a relaxed empty state.It was more about the absence of things than the presence of something.

Like a Beth state than anything else,I just can't find a better explanation.The headache/headtension got sronger,sweats were present and a somewhat upped cardiovascular.At 4hours,I suddenly started to decline and enjoyed the rest of the evening watching TV.The tension in the head remained which was a bit uncomfortable (Aspirin did help).

Sleeping was uneventful and restful.The next day was fine,somewhat foggy in the brain but I was active,cleaned the house and went for walking etc.Today,I still sense some of this head tension,altough it could be weather related.

I'm not sure if it already was a full dose,but I'll certainly try it higher as it was very enjoyable. Often I experience dark sides with dissociatives but not here.The head thing must be watched closely though (theres a BL report suspecting same about 3-HO).And I need a break first,even if its seducing me to try again...Btw I had a Ketamine shot the week before,60mg i.m.,with the usual effects.

It was like dissociative candy.If that can be a good combination...

 

[hugo24]

I love this compound,tried it at 6.2mg in one go with basically the same results,just a little stronger.The come-on first had more of that drunk feeling typical of PCP but at the peak at 2h,I felt quite straight and lucid again,nevertheless drugged,strange!It was very friendly and comfortable.Actually some tactile enhancement noted.

I'm wondering now if my jokingly made comments above about a serotonergic window has more to it?Anyone see a 5-HT "fit" in the molecule?

 

[Rectify]

hugo, ur my hero.

if meta-MeO-phenyl PCP feels like it has a 5-HT-ergic "fit" to it, then
3,4-methylenedioxy-phenyl PCP is begging to be tasted next, it seems to me.

and then 3,4,5-tri-MeO-phenyl PCP! lol. not kidding btw.

:D

 

[metaomega]

I tried 3-OH-PCPy (meta-hydroxyphenylrolicyclidine) up to 40mg with no discernable effect and if there was an effect it was close to placebo and lasted maybe 15 minutes.

Someone else tried up to 60mg with no discernable effect other than that which would be considered placebo.

Didint feel comfortable going any higher incase it was nuking neurons or someshit.

Any clue why this wasnt active or at least active anywhere near the anticipated dose range?

 

[Hammilton]

3,4-methylenedioxy-phenyl PCP is begging to be tasted next, it seems to me.
:D

yes, because that's a magical substitution and it should be tried on everything.

Phencyclidine derivatives are all reuptake inhibitors. Even if some PCP derivative had serotonergic activity, it would not be as a releaser, and as such tacking a methylenedioxy group on it makes absolutely no sense at all.

This sort of non-reasoned nonsense is what ADD needs less of. Read something and you might know exacty why these suggestions are nonsensical.

 

[hugo24]

Hammilton,but the MD-benzylamine analogs ARE active,so wait a minute with your cynism As for myself,I didn't say releaser or such,just "serotonergic".Of course a receptor screening would be very desirable here!

metaomega:really?A bit a surprise to me as the pyrrolidines are usually active.At least the title compound 1-{1-(3-Methoxiphenyl)-cyclohexyl}-piperidin has valid binding data out there,as does its OH cousin which has yet to be tried in humans.

Rectify: all unscientific guesses by me (before Hammilton gets sour again),but it has a very different feel to it.And the higher I go (8mg now tried),the more it feels like Soma has been found,or the holy rail.

Freudian Slip? The Holy Grail.

 

[Hammilton]

Hammilton,but the MD-benzylamine analogs ARE active,so wait a minute with your cynism

Which ones? Methylenedioxybenzylpiperazine? I don't know that I'd call it "active" in the sense that it's recreational.

Or wait, you mean methylenedioxy PCP derivatives?

Scifinder doesn't show any MD PCP derivatives, except for CAS: 87777-33-1, which is 1-(1-(2,2-dimethylbenzo[d][1,3]dioxol-5-yl)cyclohexyl)piperidine, for which there are a whopping two publications shown:

Analysis of phencyclidine (PCP) and other structurally related compounds by gas chromatography-mass spectrometry (GC-MS). Gole, D. J.; Pirat, J. L.; Kamenka, J. M.; Kalir, A.; Domino, E. F. Dep. Pharmacol., Univ. Michigan, Ann Arbor, MI, USA. Editor(s): Domino, Edward F.; Kamenka, Jean-Marc. Sigma Phencyclidine-like Compd. Mol. Probes Biol., [Proc. U.S.-Fr. Sponsored Int. Semin.], 2nd (1988), Meeting Date 1987, 79-89. Publisher: NPP Books, Ann Arbor, Mich CODEN: 56MCA3 Conference written in English. CAN 110:226682 AN 1989:226682 CAPLUS

Abstract

Mass spectral and gas chromatog. anal. data on PCP and 128 related compds. were compiled and categorized according to structural features. The data are available on floppy diskettes as well as illustrated as an Appendix.

Characterization of the interaction of phencyclidine and its derivatives with the ionic channel of the nicotinic receptor. Haring, R.; Theomy, S.; Kalir, A.; Sokolovsky, M. George S. Wise Fac. Life Sci., Tel Aviv Univ., Tel-Aviv, Israel. Archives of Toxicology, Supplement (1983), 6 81-90. CODEN: ATSUDG ISSN: 0171-9750. Journal written in English. CAN 99:187074 AN 1983:587074 CAPLUS

Abstract

3H-labeled-phencyclidine (PCP)(I) [77-10-1] binds specifically to the cholinergic ionophore in synaptic membranes prepd. from Torpedo elec. organ . Expts. performed by the centrifugation method establish that the binding is saturable, reversible, and selective and can be characterized by a single dissocn. const. (3.6 mM). The maximal binding capacity is 600 pmol/mg of membrane protein. Bound [3H]-PCP can be displaced by unlabeled PCP and a series of its derivs. The reactivity of PCP derivs. in binding to [3H]-PCP binding sites, as related to structural changes in the Ph, piperidyl, and cyclohexyl moieties, is discussed.

1-((1-(benzo[d][1,3]dioxol-5-yl)cyclohexyl)methyl)pyrrolidine is also known, but only one old german patent is shown. The english version is GB 973887.

I don't doubt that MDPCP derivatives are indeed active, but having any sort of MDMA like activity on serotonin? Awfully unlikely.

 

[hugo24]

MD-piperazine is a bad example as it is indeed inactive (at least up to 500mg here)-to be honest a bit of a surprise as the normal Benzylpiperazin is at least a stimulant and the piperazines allow quite some molecular changes.There was mention of an active MD-compound on BL,I thought it was of benzylic nature but the structure doesen't come to my mind now.Anyway,the point I'd like to make comes here:

In the PIHKAL entry for MDA,the alpha-Ethyl-3,4-methylendioxybenzylamine is described as active at 10mg-140mg,as is its N-methylated sister with 60mg.Body tingling,pleasant,positive feelings.The eyes-closed dreams are worth noting,part. in conjunction that its not anorexic.

Imagine the N-Ethyl homologe and you already have quite an overlap to the (3-methoxi...)PCE backbone.From MDAI (not a benzylamine) we know that a certain rigidisation and bulk is tolerated,and then compare to Tramadol which shows some NMDA antagonism with weak SRI (and NRI) properties.It looks the shoots have quite some overlap,fertile ground for searching new compounds with multiple actions.DRI is already a given on the PCP's.

I didn't propose the MD PCP and its not necessarily of high activity as a PCP/DRI substrate (the 3,4-Dimethoxi compound is known and of reduced potency),but what is known about 5-HT receptor binding resp. substrate activities of these analogs?Where are the windows here?

Well,time to read again vektors post "SAR is dead,long live SAR" and lighten up... generally, SAR/in vitro data is not too accurate in predicting subjective effects in a human and subjective effects in a human are not too accurate in predicting SAR/in vivo data.And extrapolations of existing data is dangerous.So we have to live with these dilemmas and yet advance to new frontiers.

The best way to get data is to make it a drug of abuse and let the labs make the work.

http://www.ncbi.nlm.nih.gov/pubmed/6208563