PT  - JOURNAL ARTICLE
AU  - Coccia, Peter F.
AU  - Westerfeld, W. W.
TI  - THE METABOLISM OF CHLORPROMAZINE BY LIVER MICROSOMAL ENZYME SYSTEMS
DP  - 1967 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 446--458
VI  - 157
IP  - 2
4099  - http://jpet.aspetjournals.org/content/157/2/446.short
4100  - http://jpet.aspetjournals.org/content/157/2/446.full
SO  - J Pharmacol Exp Ther1967 Aug 01; 157
AB  - The metabolic pathways by which chlorpromazine and its metabolites are transformed in vitro by rat and human liver microsomal enzyme systems were studied in detail. By use of a new method for isolating metabolites from incubation mixtures, thin-layer chromatography and radiochemical quantification, the following pathways have been demonstrated: demethylation of tertiary and secondary amine metabolites, oxidative deamination of primary amines, N-oxidation of tertiary amines, N-oxide reduction, sulfoxidation and aromatic ring hydroxylation of nonsulfoxidized metabohites at position 7 and to a lesser extent at position 3. SKF-525A inhibited all transformations except N-oxidation and N-oxide reduction. A nonenzymatic, ferrous iron-catalyzed oxidation of chlorpromazine gave ring hydroxylation at positions 7 and 3, sulfoxidation and traces of monodemethylation. Ferrous iron also catalyzed the rearrangement of the N-oxide to desmonomethyl chlorpromazine and to chlorpromazine sulfoxide, as well as the reduction of the N-oxide to chlorpromazine. © 1967 by The Williams & Wilkins Company