https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/pcp_struc.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/pcp_struc.html)
https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/sar.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/sar.html)
Has this compound ever been tested for psychoactivity? All it is is ketamine with a methyl group replacing the chlorine.
Undoubtedly Parke Davis & Co. looked at it during Ketamine development. Unfortunately their data on activity of analogs has never been published.
I'd be willing to bet that this compound is more active as a recreational drug than Ketamine though.
Unfortunately their data on activity of analogs has never been published.
I came across a couple of refs that may mention this compound . I've only looked at their abstracts so far. The papers are not specifically geared towards psychoactivity, but may contain useful info about relative binding affinitys of different analogs. If anyone looks them up, let me know about anything interesting
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Bibliographic Information
PCP receptor binding affinity predicts potency in inhibiting glutamate induced calcium accumulation in neuronal cell cultures. Coughenour, L. L.; Brahce, L. J.; Courtland, G. G.; Johnson, G.; Malone, T.; Probert, A. W.; Marcoux, F. W. Parke-Davis Pharm. Res. Div., Warner-Lambert Co., Ann Arbor, MI, USA. Neurol. Neurobiol. (1988), 46(Front. Excitatory Amino Acid Res.), 563-6. CODEN: NEUND9 ISSN: 0736-4563. Journal written in English. CAN 110:148421 AN 1989:148421 CAPLUS (Copyright 2002 ACS)
Abstract
Arylcyclohexylamine derivs. and other N-methyl-D-aspartate (NMDA) antagonists were evaluated for their affinity for the phencyclidine (PCP) receptor in rat brain membranes and for their potency in blocking 45Ca2+ accumulation in cerebral cortical neuron cultures stimulated by glutamate. There was a close correlation between the potency to inhibit [3H]thienylcyclohexylpiperidine binding to brain membranes and the potency to block glutamate-induced 45Ca2+ accumulation by cultured cortical neurons. These findings are consistent with previous data in that the affinity for the PCP site will predict the potency of the agent in producing a steric blockade of the cation channel assocd. with the NMDA subtype of the glutamate receptor.
Bibliographic Information
Local anesthetic properties of opioids and phencyclidines: interaction with the voltage-dependent, batrachotoxin binding site in sodium channels. Creveling, C. R.; McNeal, E. T.; Lewandowski, G. A.; Rafferty, M.; Harrison, E. H.; Jacobson, A. E.; Rice, K. C.; Daly, J. W. Natl. Inst. Arthritis, Diabetes, Dig. Kidney Dis., NIH, Bethesda, MD, USA. Neuropeptides (Edinburgh) (1985), 5(4-6), 353-6. CODEN: NRPPDD ISSN: 0143-4179. Journal written in English. CAN 102:214975 AN 1985:214975 CAPLUS (Copyright 2002 ACS)
Abstract
3H-labeled batrachotoxinin A 20a-benzoate (BTX-B) [78870-19-6] binds specifically and with high affinity to a site on voltage-dependent Na+ channels. Compds. with local anesthetic activity inhibit the binding of [3H]BTX-B by a mutually exclusive, allosteric mechanism. The potential local anesthetic potency of a series of 23 opioids and phencyclidine-like compds. was estd. by their inhibition of [3H]BTX-B binding to Na+ channels in a prepn. of synaptoneurosomes from guinea pig cerebral cortex. The potency of these compds. as inhibitors of the specific binding of 3H-labeled phencyclidine (PCP) [77-10-1] to a high-affinity site on rat brain membranes was also detd. Opioids such as morphine [57-27-2] and (-)-naloxone [465-65-6] show little affinity for the [3H]BTX-B binding site or for the [3H]PCP binding site. Other analgesics, many of the PCP-like compds., and dioxadrol derivs. are potent inhibitors of [3H]BTX-B binding and display both stereospecificity and high affinity towards the PCP-binding site. However, there was no correlation between local anesthetic potency (assessed as antagonism of [3H]BTX-B binding) and affinity towards the PCP site. Five classical local anesthetics had no affinity for the PCP site, but did displace [3H]BTX-B from its binding site.
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A 2-methyl should be a favorable substitution in these compounds though. In JMC 1990 33, 1452-1458, the addition of a 2-methyl to phenylcyclohexylamine increased its potency. It is interesting that ketamine has a 2-chloro, since this probably decreases binding affinity. The 2-chloro may enhance speed of penetration into the CNS though, which is a more important property in an anesthetic.
Its the 4-methyl compound that bothers me though. Several papers have suggested that it has lower potency in receptor binding assays. But I'd like to see a more personal approach to evaluating it.
https://www.thevespiary.org/rhodium/Rhodium/pharmacology/pcp.nmda.not.sigma1.html (https://www.thevespiary.org/rhodium/Rhodium/pharmacology/pcp.nmda.not.sigma1.html)