Perazine,chlorpromazine and imipramine as inducers of microsomal drug metabolism

Summary Male rats were treated orally for 7 days with perazine, chlorpromazine, imipramine or phenobarbital. Isolated liver microsomes were tested for their metabolic activities towards perazine, ethylmorphine and aniline. N-Demethylation of perazine and ethylmorphine was increased 2–3.5 fold by all pretreatments. Aromatic hydroxylation of perazine was decreased in microsomes from pretreated animals, whereas aniline hydroxylation was enhanced even more by perazine and imipramine than by phenobarbital. The yield of perazine sulfoxide was increased by phenobarbital treatment only. Perazine N-oxide formation was reduced by treatment with psychoactive drugs to 75–90% of control values and by phenobarbital to less than 50%. The microsomal cytochrome P-450 concentration was slightly elevated by perazine and substantially by chlorpromazine and imipramine treatment. The tricyclic drugs investigated are potent inducers of the drug-metabolizing enzyme system, the induction pattern differing in some respects from that seen after phenobarbital.