The Big & Dandy 4-MeO-PCP Thread

[Ham-milton]

link is useless.

 

[immaturepoop]

The only way I know of getting the methoxy group on the cyclohexane ring would be to start the synth with it already there. I guess since it's an alkane you could start with just the cyclohexane ring and use a radical halogenation reaction using Br2/uv light and then follow with a substitution reaction using MeO(-) using NaH and methanol (or sodium methoxide), but it seems more trouble then its worth...

In the above reaction - the picture is kinda small - but it looks like a grignard reagent reaction with an alcohol. I don't think that is possible, unless I'm looking at it wrong.

 

[vecktor]

as has been pointed out the 4-methoxy in this refers to the phenyl ring, 4-meoPCP is a known metabolite of PCP. (IUPAC was not always god.) as is 4-OH PCP. 4-meo is obtained through the methoxy grignard or lithium either through the PCC route shown above or through the enamine. proper name is 1-(1-(4-methoxyphenyl)cyclohexyl)piperidine. the older naming conventions used 4' and 4'' to refer to the other rings but I don't remember which is which

Any non competitive NMDA antagonist (channel blocker) that doesn't also sedate and massively reduce motor co-ordination is a disaster waiting to happen, search youtube for PCP and you'll see why, for some reason one of the common effects of pcp seems to involve nekkidness and tasers. ketamine has this built in safety mechanism.

As someone who likes (liked) ketamine I have a question, Did anyone come to a definitive conclusion about olneys lesions and NMDA antagonist neurotoxicity in humans as oppoesed to rats and mice?
I suspect that the non-competitive NMDA antagonists cause problems, Ketamine seemed to do a pretty good job of fucking up Lilly whereas Leary (psychedelics mostly) was compos mentis until the end.

 

[<pyridinyl_30>]

There is no doubt in my mind that ketamine is moderately to highly neurotoxic in humans as well. This observation is based on my own personal experience.

A 1 gram vial bottle--1.2g actually (83% pure ketamine.hcl)--consumed by me (either insuffulated or injected intramuscularly) over one or two days gives me dark, violent thoughts afterwards and makes me prone to outrageous behavioral outbreaks for up to six months afterwards. Think James Brown.

Of course, you could blame all that on me and call me crazy, and you're welcome to do just that if you wish, but what about Michael Alig? Look what he did after abusing ketamine heavily. (He murdered the dealer who owed him money by dismemberment.)

I'm not claiming absolute causality or blaming the drug, but ketamine in my experience is the most toxic drug I've done along with thujone, much more so than pure amphetamines, cocaine, the 2c's, marijuana, magic mushrooms, or MDMA. It's a dark trip.

I cringe when presumably drug naive scientists call ketamine "neuroprotective" while labeling MDMA "neurotoxic." What a crock of shit.

If you still don't believe ketamine use, even one time use, can induce what is dubbed "emergent psychosis," then check out ketamine's side effect profile in any edition of the Physician's Desk Reference. Luckily, Zyprexa (olanzapine) is one of the few medications which have been shown to alleviate this syndrome.

Furthermore, I have observed mild to moderate cognitive impairment for months after ketamine abuse similar to that induced by dextromethorphan overuse. I'm not telling anyone not to do ketamine or anything like that, but I can only imagine how neurotoxic ortho-chlorophenyl-pcp would be after experiencing ketamine many, many times.

On the other hand, ketamine is subtly reinforcing in an other worldly, sedating way and can easily appeal to one's escapist tendencies; also, "magical" is quite an apt word for its effects.

I would actually love to try 1-dimethylamino-1-phenylcyclohexane, but I doubt have any false notions that it isn't at least somewhat harmful to one's neurochemistry and, possibly, one's neuromorphology.

 

[LuxEtVeritas]

well doses well below rec for KET are i believe indeed neuroprotective or is that mistaken, just to clarify that of course context (dose) needs to be accounted for

has anyone heard of what very high dose memantine produces effect-wise and safety...i think i have seen some account of this but do not recall offhand

looking at that TCP and GK11 it appears perhaps they may have a similar effect at a dose that does not engender the neurotoxicity of KET

of course there are also some agents that seem at the right dose and administration for some can bear a reasonable nice resemblance to a nice K trip or so I am told such as quality Sub-L Salvinorin A

anyway ....food for thought

 

[LuxEtVeritas]

ooops...sorry for the continuation of a hijack of sorts though the exporation of safe/safer NMDA anatgonists should be of some interest to those attracted to the thread %)

 

[IlostaMadge]

Cheers to the people who corrected the structure .

Of course, you could blame all that on me and call me crazy, and you're welcome to do just that if you wish, but what about Michael Alig? Look what he did after abusing ketamine heavily. (He murdered the dealer who owed him money by dismemberment.)

It's your fault and you are crazy! I do not think however that crazy behaviour is a sign of neurotoxicity, ketamine and indeed all dissociatives carry a very delusional edge to them, think about the amount of coincidences you see after heavy K or DXM use (reported by a lot of users), this is more psychological degeneration than neurotoxicity in my eyes (I'm fairly sure they are different).

I cringe when presumably drug naive scientists call ketamine "neuroprotective" while labeling MDMA "neurotoxic." What a crock of shit.

Ket is going to be/is currently in pharmaceutical investigation for AD effects, we should get some more conclusive proof on neurotoxicity from that.

Magnesiums insane neurotoxicity at high dose levels scares me, could this be the same albeit greatly enhanced neurotoxic mechanism as the other NMDA antagonists?

Any non competitive NMDA antagonist (channel blocker) that doesn't also sedate and massively reduce motor co-ordination is a disaster waiting to happen, search youtube for PCP and you'll see why, for some reason one of the common effects of pcp seems to involve nekkidness and tasers. ketamine has this built in safety mechanism.

I think this is partly/mostly down to PCP breaking down to piperidine and PC (I think it's PC) when smoked, ever done ket alongside a hard stimulant? It gets freaky.

As someone who likes (liked) ketamine I have a question, Did anyone come to a definitive conclusion about olneys lesions and NMDA antagonist neurotoxicity in humans as oppoesed to rats and mice?

I read that was retracted by the author as it was never established in humans or chimps, and was most likely down to the massively increased metabolism exhibited by our rodent chums.

 

[fastandbulbous]

I do not think however that crazy behaviour is a sign of neurotoxicity, ketamine and indeed all dissociatives carry a very delusional edge to them, think about the amount of coincidences you see after heavy K or DXM use (reported by a lot of users), this is more psychological degeneration than neurotoxicity in my eyes (I'm fairly sure they are different).

Totally different creatures - MPTP is hideously neurotoxic, but it doesn't drive you crazy (although having just about the worst case of Parkinson's ever seen is not going to be a barrel of laughs)

I cringe when presumably drug naive scientists call ketamine "neuroprotective" while labeling MDMA "neurotoxic." What a crock of shit.

Well colour me a naive drug scientist as ketamine prevents glutamate induced excitotoxicity in nerve cells deprived of oxygen - MDMA has no such effects and the neurotoxicity of the compound due to serotonogic neurones reuptaking dopamine and being damaged by subsequent free radical formation is well established. The long term cognative defects seen with prolonged, heavy ketamine use seem more a product of repeatedly having concensus reality broken down to it's fundamental components rather than any biochemical neurotoxic effects (well in my opinion anyway)

has anyone heard of what very high dose memantine produces effect-wise and safety...i think i have seen some account of this but do not recall offhand

Well considering it's a close derivative of amantadine, which is quite a nasty drug in excess/overdose, I don't think I'd be chomping down a large dose of memantine in the forseeable future, no matter how much of a liking I have for dissociatives

I think this is partly/mostly down to PCP breaking down to piperidine and PC (I think it's PC) when smoked, ever done ket alongside a hard stimulant? It gets freaky.

It's actually PCC - phenylcyclohexylcarbonitrile - and as far as I'm aware it's not a pyrolysis breakdown product but a contaminant from the synthesis (illicit drug manufacturers aren't that big on quality control for the most part!). After having experienced PCP, I'd think the neurotoxicity associated with PCP is due to the massively OTT dopaminergic activity (again the dopamine/free radical connection). Ketamine only has a fraction of the dopaminergic activity of PCP

 

[egore]

Hope this helps>

In vivo functional interaction between phencyclidine binding sites and sigma receptors to produce head-weaving behavior in rats.Kitaichi K, Noda Y, Hasegawa T, Furukawa H, Nabeshima T.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Japan.

"To investigate the in vivo functional interaction between phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP) binding sites and sigma receptors, we examined the effects of sigma receptor ligands on stereotyped head-weaving behavior induced by PCP, a putative PCP/sigma receptor ligand, and (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imin e ((+)-MK-801; dizocilpine), a selective PCP binding site ligand, in rats. PCP (7.5 mg/kg, i.p.)-induced head-weaving behavior was inhibited by both N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine (NE-100; 0.03-1.0 mg/kg, p.o.), a selective sigma1 receptor ligand, and alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperidine butanol (BMY-14802; 3 and 10 mg/kg, p.o.), a prototype sigma receptor ligand, in a dose-dependent manner, whereas NE-100 (0.1-1.0 mg/kg, p.o.) and BMY-14802 (3 and 10 mg/kg, p.o.) did not inhibit dizocilpine (0.25 mg/kg, s.c.)-induced head-weaving behavior. These results suggest that NE-100 and BMY-14802 act via sigma receptors. Dizocilpine-induced head-weaving behavior was potentiated by 1,3-di-o-tolyl-guanidine (DTG; 0.03-0.3 microg/kg, i.v.) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP; 3 and 6 mg/kg, i.p.), sigma1/sigma2 receptor ligands, as well as by (+)-N-allyl-normetazocine ((+)-SKF-10,047: 8 mg/kg, i.p.), a sigma1 receptor ligand, while DTG (0.3 microg/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) did not induce this behavior. Potentiation of dizocilpine-induced head-weaving behavior by DTG (0.3 microg/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) was completely blocked by NE-100 (0.1 mg/kg, p.o.) and BMY-14802 (10 mg/kg, p.o.). These results suggest that PCP binding sites and sigma receptors are involved in PCP-induced head weaving behavior, and that sigma1 receptors play an important role in modulation of the head-weaving behavior."

 

[PhreakEDIT]

For a lab monkey, what would be a reasonable 'starter' dose for this analogue, insufflated or smoked...?

Due to its relative potency to its cousin PCP (about 75%), am I right in thinking a "light" dose would be around 7mg?

 

[hamhurricane]

^^^
take a small amount to test for idiosyncratic reactions and then i would start with a dose no higher than 5mg unless you are very comfortable with dissociatives, when you take it PLEASE report back here or post a TR, as there is virtually no info on this chem.

 

[PhreakEDIT]

I am very comfortable with disocciatives - Ket is my favourite drug of all time and nothing (except maybe a deeply philosophical and visually stunning 'shroom trip) beats a K-Hole.

HOWEVER, this is a stimulating disocciative which is a bit weird. I didn't like DXM - it feels kind of grimey - but then again no other disocciative actually generates euphoria (Ketamine may make you feel euphoric, but it's only from being content/astounded by the experience), whereas PCP gives you chemically induced euphoria. I'm not sure about the analogue, but I assume it's the same.

I will try 0.5mg or something to test for allergies/idiosyncratic effect before hand...

And yes, I already plan to write up a very, very detailed trip report on this stuff. One whilst I'm on it (not live, just notes that I can order later) and one objective one afterwards. There is so little info out there on this stuff and I feel quite happy that I'll be able to provide insight for others...

I will have a report done in....let's say 4 days; just in case something else comes up that takes priorty (damn work).

 

[Coolio]

Ketamine has pronounced euphoria, I don't know where you got the impression it didn't. Ketamine is a dopamine reuptake inhibitor like cocaine.

 

[Hammilton]

Stereoselective effects of ketamine on dopamine, serotonin and noradrenaline release and uptake in rat brain slices

Michelle M. Tso, Karen L. Blatchford, Luis F. Callado, Daniel P. McLaughlin and Jonathan A. Stamford,

Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, Barts and The London School of Medicine and Dentistry, Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, UK


Received 6 January 2003; revised 4 March 2003; accepted 5 March 2003. ; Available online 13 May 2003.

Abstract
Ketamine (2-(2-chlorophenyl)-(1-methylamino)-cyclohexanone) is a rapid-acting dissociative general anaesthetic whose hallucinogenic properties have made it a popular drug of abuse. Ketamine comprises two optical isomers, with differing pharmacology. In the present study, the effects of (+)- and (−)-ketamine on stimulated efflux and reuptake of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were compared in isolated superfused slices of the rat caudatoputamen (CPu), ventral bed nucleus of the stria terminalis (BSTV) or dorsal raphe nucleus (DRN), respectively. Monoamine efflux was elicited by local electrical stimulation (20 pulses, 100 Hz trains) at tungsten microelectrodes and measured at adjacent carbon fibre microelectrodes using fast cyclic voltammetry (FCV). In CPu (+)-ketamine increased stimulated DA efflux and slowed DA reuptake in a concentration-dependent manner (25–200 μM). At 100 μM (+)-ketamine increased DA efflux by 109±20% (mean±S.E.M., n=13) of control values after 30 min (P<0.001 versus control) and prolonged uptake half-time (t1/2) by 76±38% (n=9, P<0.001) of control. In contrast (−)-ketamine (100 μM) had no effect on DA efflux or uptake. In DRN, both isomers (100 μM) increased stimulated 5-HT efflux. (−)-Ketamine had a larger effect (P<0.001), an 88±15% increase in 5-HT efflux (n=9) versus 46±10% (n=8) for the (+)-isomer. The isomers had similar effects on 5-HT uptake, increasing t1/2 by approximately 200%. No evidence of stereospecificity was seen in BSTV: both isomers had small effects (+)- and (−)-ketamine (100 μM) increasing NA efflux by 43±10% (n=7, P<0.001) and 29±8% (n=7, P<0.001), respectively. The isomers also had identical effects on NA uptake, each increasing uptake t1/2 by approximately 100%. In summary, our data show that the optical isomers of ketamine have strikingly different stereospecificity for the monoamine systems and one might predict, therefore, a different psychotomimetic potential.

Ketamine isn't a very strong DARI, but it is really interesting, imho that (-)-ket preferentially releases 5HT, but both release 5HT, but (+)-ket is the only side with real DA effects.

 

[theWorldWithin]

Well colour me a naive drug scientist as ketamine prevents glutamate induced excitotoxicity in nerve cells deprived of oxygen - MDMA has no such effects and the neurotoxicity of the compound due to serotonogic neurones reuptaking dopamine and being damaged by subsequent free radical formation is well established. The long term cognative defects seen with prolonged, heavy ketamine use seem more a product of repeatedly having concensus reality broken down to it's fundamental components rather than any biochemical neurotoxic effects (well in my opinion anyway)

I could be mixing up my facts here but Ketamine is most definitely neurotoxic in humans at recreational doses. Only a full anesthetic dose shuts down NMDA receptors and exerts a neuroprotective effect. All recreational K experience falls into the sub-anesthetic dosage range at which it significantly excites NMDA receptors thus causing the excitotoxicity that many claim it cures. The only real question is to what extent if any are olneys legions happening in primates, but neurotoxicity is definitive.

Now explaining how wacked out people get after K is anyones guess. I think its a combination of detachment from consensual reality coupled with neuroplastic changes. There is little doubt that neuroplasticity is significant when one considers the severe verbal impairment and learning disabilities suffered by K addicts. But really it makes little difference why it happens (outside of acedemic speculation) because I still will not be putting any of that shit up my nose in the future. Really fun drug but definitely has medium term negative effects.

 

[Tranced]

I will try 0.5mg or something to test for allergies/idiosyncratic effect before hand...

And yes, I already plan to write up a very, very detailed trip report on this stuff. One whilst I'm on it (not live, just notes that I can order later) and one objective one afterwards. There is so little info out there on this stuff and I feel quite happy that I'll be able to provide insight for others...

I will have a report done in....let's say 4 days; just in case something else comes up that takes priorty (damn work).

I very much look forward to this. Will probably follow suit depending on results.

 

[nuke]

I could be mixing up my facts here but Ketamine is most definitely neurotoxic in humans at recreational doses. Only a full anesthetic dose shuts down NMDA receptors and exerts a neuroprotective effect. All recreational K experience falls into the sub-anesthetic dosage range at which it significantly excites NMDA receptors thus causing the excitotoxicity that many claim it cures. The only real question is to what extent if any are olneys legions happening in primates, but neurotoxicity is definitive.

Probably not true. The doses with rats in which vacuolisation occurred was beyond that used with humans (40mg/kg). Experiments with simian species and humans have not been able to establish anything close to neurotoxicity with most NMDA antagonists. Further, the damage seems to be dose dependent:

These changes do not appear to be a prelude to irreversible damage except after relatively high doses of the receptor ion channel antagonists but they have given rise to concern over the safety in use of NMDA antagonists as neuroprotective agents.

http://www.ncbi.nlm.nih.gov/pubmed/7976530

However, if you're really concerned, you may only want to do ketamine after you've dropped a lot of acid too:

Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity.
Farber NB, Hanslick J, Kirby C, McWilliams L, Olney JW.

Department of Psychiatry, Washington University, St. Louis, Missouri, USA.

Phencyclidine, ketamine, and other agents that block NMDA glutamate receptors trigger a schizophrenia-like psychosis in humans and induce pathomorphological changes in cerebrocortical neurons in rat brain. Accumulating evidence suggests that a complex network disturbance involving multiple transmitter receptor systems is responsible for the neuronal injury, and it is proposed that a similar network disturbance is responsible for the psychotomimetic effects of NMDA antagonists, and might also be involved in the pathophysiology of schizophrenia. In the present study we present evidence that serotonergic agents possessing 5HT2A agonist activity prevent NMDA antagonist neurotoxicity in rat brain. It is proposed that 5HT2A agonists may also prevent the psychotomimetic effects of NMDA antagonists. Among the 5HT2A agonists examined and found to be neuroprotective are LSD and related hallucinogens. The apparent contradiction in proposing that these agents might have antipsychotic properties is resolved by evidence linking their hallucinogenic activity to agonist action at 5HT2C receptors, whereas antipsychotic activity would be attributable to agonist action at 5HT2A receptors.

http://www.ncbi.nlm.nih.gov/pubmed/9408919

 

[Coolio]

Any human trials yet?

 

[Tranced]

Just the one who disappeared.

Hope he's not dead.

 

[PhreakEDIT]

Still haven't got mine yet. I'll do a report whenever I do.

And can people stop PM-ing me please - I can't reply! I have to have a certain post count or something. I'm not being rude, I'm just not established here enough yet.