Interactions of iprindole with fenfluramine metabolism in rat brain and liver

An assay procedure utilizing electron-capture gas chromatography was developed for simultaneous analysis of fenfluramine and norfenfluramine. This method was applied to brain and liver samples from rats which had been injected with fenfluramine with or without pretreatment with iprindole. The tissue...

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Bibliographic Details
Published in:Journal of psychiatry & neuroscience 1991-03, Vol.16 (1), p.5-11
Main Authors: Hegadoren, K M, Baker, G B, Coutts, R T, Dewhurst, W G
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Brain - metabolism
Brain Chemistry - drug effects
Chromatography, Gas
Drug Interactions
Fenfluramine - metabolism
Fenfluramine - pharmacology
Iprindole - metabolism
Iprindole - pharmacology
Liver - chemistry
Liver - drug effects
Liver - metabolism
Norfenfluramine - metabolism
Rats
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Summary:An assay procedure utilizing electron-capture gas chromatography was developed for simultaneous analysis of fenfluramine and norfenfluramine. This method was applied to brain and liver samples from rats which had been injected with fenfluramine with or without pretreatment with iprindole. The tissues from rats treated with fenfluramine showed extensive formation of norfenfluramine, consistent with findings reported previously in the literature. Pretreatment with iprindole led to an increase in brain and liver levels of fenfluramine, and, unexpectedly, to a marked decrease in levels of norfenfluramine in these tissues. These findings suggest that iprindole blocks N-deethylation and that it may be a useful tool with which to study the effects of fenfluramine in the absence of norfenfluramine. The results also emphasize the importance of considering drug-drug interactions in future research on fenfluramine.
ISSN:1180-4882
1488-2434