Document Detail


Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine: a multi-functional model substrate.
MedLine Citation:
PMID:  2805159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Masumoto; K Takeuchi; S Ohta; M Hirobe
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  37     ISSN:  0009-2363     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  1989 Jul 
Date Detail:
Created Date:  1989-12-12     Completed Date:  1989-12-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  1788-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytochrome P-450 Enzyme System / metabolism*
Male
Microsomes, Liver / enzymology
NADP / metabolism
Phencyclidine / metabolism*
Rats
Rats, Inbred Strains
Substrate Specificity
Chemical
Reg. No./Substance:
53-59-8/NADP; 77-10-1/Phencyclidine; 9035-51-2/Cytochrome P-450 Enzyme System

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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