P.1.c.010 Gender-dependent influence of bupropion pretreatment on locomotor activity and the activity of hepatic CYP2D2 in rats
2007
One of the most important enzymatic systems participating in
drug metabolism is cytochrome P450 (CYP450). CYP450 consists of
many isoforms which activity of is influenced by numerous
endogenous (e.g. gender, pathophysiological status, age) and
exogenous factors (e.g. xenobiotical inhibitors and inducers).
Although bupropion is not metabolized by CYP 2D6 (human
ortologue of rat CYP2D2), there is certain potential for
interaction when bupropion is co-administered with other drugs
metabolized by this isoenzyme, too. The aim of the present
study was to determine the influence of gender and
administration of bupropion on the CYP450 isoform 2D2 (CYP2D2)
activity. As selective markers of the metabolic activity of
CYP2D2 dextromethorphan (DEM) and its metabolite dextrorphane
(DOR) were used. In animals treated with bupropion compared to
control animals administered with saline the inhibitory effect
of bupropion was expressed as a decrease of DOR in the 30th,
60th and 120th minutes of perfusion. The influence of gender on
locomotor activity has shown that activity in intact females
were similar as in the intact males. In the bupropion treated
animals females were significantly more active in subsequent
open field tests then in males.
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