The metabolism of phencyclidine by rabbit liver preparations

The in vitro metabolism of phencyclidine by rabbit liver 9000g supernatant fraction produces primarily three known hydroxylated metabolites-namely, 4-phenyl-4-piperidinocyclohexanol, 4-(4'-hydroxypiperdino)-4phenylcyclohexanol, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine-plus a new metabolite formed by oxidative scission of the piperidine ring yielding an aminoalcohol, and much smaller amounts of five unidentified metabolites. Incubation with 50% deuterium-labeled PCP indicates that these compounds are metabolites by monitoring the resulting doublets found in their mass spectra. The time, cofactor, and protein-dependent formation of these compounds confirms that they are indeed, metabolites. DPEA inhibits the production of the four quantitated metabolites with maximal I50 values of approximately 50 microM, implying the involvement of cytochrome P-450 in these reactions.