title: Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine: a multi-functional model substrate.
abstract: Cytochrome P450 model and liver microsomal oxidations of drugs were compared using phencyclidine. In general, the chemical reaction systems produced many oxidation products. Besides the formation of the cyclohexane-4-hydroxyl compound (2), hydroxylation of the aromatic ring was favored in the Fenton reaction system (Fe2+ + H2O2). Formation of an m-hydroxylated product (m-5) was the main aromatic oxidation pathway in the Udenfriend reaction (Fe2+-ascorbic acid-O2), and 2, the piperidine-3-hydroxyl compound (3), and the piperidine-4-hydroxyl compound (4) were also formed. In the system using meso-tetraphenylporphinatoiron chloride (Fe(III)TPPC1) with an oxidant, the main product was the piperidine-3-oxo compound (8). In the liver microsomes system, 2, 4, 8, and m-5, which were all generated by the chemical oxidation reactions, were detected as metabolites of phencyclidine. They were formed by cytochrome P450-dependent reactions. Chemical oxidation systems can be used to study drug metabolism; they can reveal some tendencies of the real metabolic reactions, are easy to operate, and yield sufficient amounts of product.
authors: H
authors: H
authors: Masumoto
authors: K
authors: K
authors: Takeuchi
authors: S
authors: S
authors: Ohta
authors: M
authors: M
authors: Hirobe
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
chemical_list: D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010622:Phencyclidine