The effect of imipramine and desipramine on mixed function oxidase in rats

The effects of imipramine and desipramine on hepatic mixed function oxidase were measured in male Wistar rats. Both antidepressants increased hepatic cytochrome P-450 when given b.i.d. for 7 or 14 days. In vitro demethylation of imipramine was rather depressed than increased. 14CO2 exhalation from [N-methyl-14C] benzphetamine was increased by pretreatment with the antidepressants as well as with phenobarbital, but imipramine had no influence on the exhalation of the label from [6-methoxy-14C]- or [7-methoxy-14C]-scoparone. No difference was observed between treatment with imipramine or desipramine. It is concluded that changes of the demethylation rate of imipramine are not responsible for its delayed elimination observed after chronic treatment (Daniel et al. 1981).