3-HO-PCP and Opioid Affinity

[bjznoviskey]

I know this comes up here and there, I was trying to find where I originally posted that I would come back with old studies but I couldn't :/ soooo.... here I am. I apologize if these have been posted before and it' an old subject but I figured it couldn't hurt. Sorry, some aren't all that accessible.

http://archives.drugabuse.gov/pdf/monographs/75.pdf#page=196 - Yossef Itzhak. NIDA Research Morograph. 1986. 75. 173-176. 2828967.

http://pubs.acs.org/doi/abs/10.1021/jm00346a019 - J. M. Kamenka, B. Chiche, R. Goudal, P. Geneste, J. Vignon, J. P. Vincent, M. Lazdunski. Journal of Medicinal Chemistry. April 1982. 25. 4. 431–435. 10.1021/jm00346a019. 6279847.

http://www.sciencedirect.com/science/article/pii/0014299981900972 - Yossef Itzhak, Asher Kalir, Yosef Sarne. European Journal of Pharmacology. July 1981. 73. 2–3. 229–233. 10.1016/0014-2999(81)90097-2. 6273187.

http://www.sciencedirect.com/science/article/pii/0014299984901717 - Nicole Johnson, Yossef Itzhak, Gavril W. Pasternak. European Journal of Pharmacology. June 1984. 101. 3–4. 281–284. 10.1016/0014-2999(84)90171-7. 6088255.

http://www.sciencedirect.com/science/article/pii/0024320588906467 - Yossef Itzhak. Life Sciences. 1988. 42. 7. 745–752. 10.1016/0024-3205(88)90646-7. 2893238.

http://www.sciencedirect.com/science/article/pii/0014299987907151 - Yossef Itzhak. European Journal of Pharmacology. April 1987. 136. 2. 231–234. 10.1016/0014-2999(87)90715-1. 3036548.

 

[palmanita]

I am very interested in this too. Particularly because of 3-HO-2'-OxO-PCE appears to be a metabolite of MXE (in rats probably, there is a paper about the metabolism somewhere). Could apply to the other 3-MeOs too?

And once I've had a small sample of either 3-HO-PCE or PCP, unfortunately I don't remember which one. It had an unique sort of stoning, relaxing effect that I couldn't categorize. Have to say that I'm an atypical opioid non responder though, I get next to no reward out of opioids (yeah, didn't believe this for myself long time but it's the case.)

 

[clubcard]

I think you need a ketone on the para (4) position of the cyclohexane ring. Just shows that the N & O lone-pairs can be swapped in opioids (BDPC being the most well known but there are a large number of others - so long 'Morphine Rule'.

 

[palmanita]

All I can say is that subjectively both 3-MeO-2'-OxO-PCE (Methoxetamine) and 3-MeO-PCE exhibit robust serotonergic effects combined with at least moderate opioid activity. This might be dependent on the individual metabolism, but I see/feel clear similarities between e.g. Codeine and MXE. The opioid effect sets in with some delay, indicating that a metabolite is responsible for. It's a quality of effect that for example ketamine doesn't share.

But can it be that this is from endorphin release / potentiation through the NMDA antagonism?

clubcard, so one would need 4'-OxO-PCE for example to get an opioid? Is there possibility that the 2'-OxO ones have low affinity too?

 

[serotonin2A]

But can it be that this is from endorphin release / potentiation through the NMDA antagonism?

It may reflect a convergence of downstream effects. Ketamine and other arylcyclohexylamines inhibit a channel known as HCN, which is also inhibited by the mu opioid receptor. Inhibiting the channel seems to produce sedative effects, which may have an opioid-like feel.

Assessing subjective responses can give you some insight into pharmacology but is fraught with pitfalls. A more reliable way to assess opioidmimetic effects is by testing whether these compounds reliably suppress opioid withdrawal. Unfortunately, that doesn't seem to be the case.

 

[clubcard]

I found a K derivative patent with a 2-chloro-5-methoxy K. Now, how many patents cover just 1, specific compound?