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 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.
Hegadoren
K M
KM
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Coutts
R T
RT
Dewhurst
W G
WG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002849:Chromatography, Gas; D004347:Drug Interactions; D005277:Fenfluramine / Q000378:metabolism / Q000494:pharmacology*; D007488:Iprindole / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009642:Norfenfluramine / Q000378:metabolism; D051381:Rats
D009642:Norfenfluramine; D005277:Fenfluramine; D007488:Iprindole