Effect of neuroleptics on cytochrome P450 2C11 (CYP2C11) in rat liver
Abstract
The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of cytochrome P450 2C11 (CYP2C11), measured as a rate of testosterone 2α- and 16α-hydroxylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in the microsomes of rats treated intraperitoneally (ip) with pharmacological doses of the drugs (promazine, levomepromazine, thioridazine and perazine 10 mg/kg; chlorpromazine 3 mg/kg; haloperidol 0.3 mg/kg; risperidone 0.1 mg/kg; sertindole 0.05 mg/kg) for one day or two weeks (twice a day), in the absence of the neuroleptics in vitro. The investigated neuroleptics added to control liver microsomes produced some inhibitory effects on CYP2C11 activity, which were moderate (thioridazine: K(i) = 55), modest (sertindole and perazine: K(i) = 76 and 94 μM, respectively) or week (promazine, levomepromazine, haloperidol and chlorpromazine: K(i) = 285, 280, 223 and 157 μM, respectively). Risperidone had the weakest inhibitory effect on the CYP2C11 activity (K(i) = 641 μM). One-day exposure of rats to the neuroleptics did not significantly change the activity of CYP2C11 in liver microsomes. Of the neuroleptics studied, only chronic ...Continue Reading
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