Phencyclidine metabolism: resolution, structure, and biological activity of the isomers of the hydroxy metabolite, 4-phenyl-4-(1-piperidinyl)cyclohexanol.
One of the major biotransformation pathways in the metabolism of phencyclidine is hydroxylation at C-4 of the cyclohexane ring to give 4-phenyl-4-(1-piperidinyl)cyclohexanol (1). Since the latter compound can exist as cis and trans isomers and the synthetic mixture has been reported to be biologically active, it was of interest to separate the isomers, test them for biological activity, and determine their ratio as metabolic products of phencyclidine. The synthetic mixture of 1 was separated by TLC and the individual isomers were characterized by 13C and 1H NMR and MS analyses. Preliminary testing of the isomers in the mouse rotarod assay indicates that the trans isomer (1b) is only slightly more active then the cis isomer (1a). Both isomers produced seizure activity and lethality at doses required to produce maximal ataxia.
D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001711:Biotransformation; D004285:Dogs; D006900:Hydroxylation; D008297:Male; D051379:Mice; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced; D013045:Species Specificity; D013237:Stereoisomerism
C031107:4-phenyl-4-piperidinocyclohexanol; D010622:Phencyclidine