The effects of 1-alkylimidazoles on hepatic drug-metabolizing enzyme activity

Abstract

1. Certain 1 -alkylimidazoles, containing a C₈-C₁₅ alkyl group, are potent inhibitors of liver microsomal drug oxidations. At a concentration of 10₋₄M, they inhibited almost entirely the aminopyrine demethylase activity of rat liver 10 000 g supernatant fraction. In vivo, they prolonged hexobarbitone sleeping time in mice.

2. Inhibition of aminopyrine demethylase by 1-geranylimidazole was of a mixed type at high inhibitor concentrations and noncompetitive at low concentrations.

3. Addition of 1-geranylimidazole to rat liver microsomal fraction elicited a type II spectral change, but the use of hexobarbitone as a modifier revealed both type I and type II components.

4. Rats killed 24 h after the last of eight daily (100 mg/kg) doses of 1-do-decylimidazole showed marked induction of aminopyrine demethylase and aniline hydroxylase activities, but no change in cytochrome P-450 level.