Formation of chlorpromazine sulphoxide and monodesmethylchlorpromazine by microsomes of small intestine

The metabolism of chlorpromazine by microsomal preparations of the small intestine from guinea pig and rat was studied. 35S-chlorpromazine was incubated with these preparations in Krebs-Ringer bicarbonate buffer at 37 degrees C. Control values were obtained by performing the assay at 0 degrees C. Th...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1977-03, Vol.297 (2), p.195-200
Main Authors: Knoll, R, Christ, W, Müller-Oerlinghausen, B, Coper, H
Format: Article
Language:English
Subjects:
Animals
Chlorpromazine - metabolism
Cytochrome P-450 Enzyme System - analysis
Female
Guinea Pigs
Intestine, Small - metabolism
Intestine, Small - ultrastructure
Microsomes - metabolism
Oxidoreductases, N-Demethylating - metabolism
Rats
Sulfoxides - metabolism
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Summary:The metabolism of chlorpromazine by microsomal preparations of the small intestine from guinea pig and rat was studied. 35S-chlorpromazine was incubated with these preparations in Krebs-Ringer bicarbonate buffer at 37 degrees C. Control values were obtained by performing the assay at 0 degrees C. The metabolites were extracted with dichloroethane and separated by TLC. In incubations with intestinal microsomes from guinea pigs chlorpromazine sulphoxide and monodesmethyl chlorpromazine were identified as main metabolites. The apparent Michaelis constant for sulphoxidation of chlorpromazine is approximately 20-30 micronM and for N-demethylation in the range of 30-100 micronM. Using microsomal preparations from rat intestine, however, noteworthy formation of chlorpromazine metabolites could not be found. This observation can be explained by the fact that the cytochrome P450 content of rat intestinal microsomes was extremely low compared with that determined in guinea pig microsomes.
ISSN:0028-1298
1432-1912
DOI:10.1007/BF00499931