Induction of phencyclidine metabolism by phencyclidine, ketamine, ethanol, phenobarbital and isosafrole.
The in vitro metabolism of phencyclidine (PCP) was investigated in 9000 g supernatant fractions of both control and PCP-, ketamine-, ethanol-, phenobarbital- or isosafrole-pretreated rats. Levels of PCP, trans-4-phenyl-4-piperidinocyclohexanol (I), 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (II), N-(5-hydroxypentyl)-1-phenylcyclohexylamine (IX), and 5-(1-phenylcyclohexylamino)-valeric acid (X) were monitored by gas chromatographic analysis in all cases. The inhibition of metabolism by N2, CO, SKF-525A or 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), or deletion of NADPH or protein, implied the involvement of cytochrome P-450 in the reactions. The various inducing agents affected the metabolism of PCP in different ways, implying that at least several isozymes of cytochrome P-450 were involved in the total metabolism. The majority of the consumed PCP was not accounted for by the measured metabolites so that some other metabolic pathways of major quantitative importance must be operative.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004149:Dioxoles / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism* / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000494:pharmacology*
D004149:Dioxoles; D000431:Ethanol; D007649:Ketamine; D003577:Cytochrome P-450 Enzyme System; D010622:Phencyclidine; D012451:Safrole; C015959:isosafrole; D010634:Phenobarbital