Abstract
1-(2-Isopropylphenyl)imidazole and 1-(2-cyanophenyl)imidazole are inhibitors of several oxidative drug-metabolizing enzyme systems in rat liver microsomes. The inhibition of the p-hydroxylation of aniline and acetanilide is competitive, while that of the N-demethylation of aminopyrine is noncompetitive. The more potent compound, the isopropyl derivative, has Ki values as low as 0.5 µM against some substrates. This derivative also prolongs and intensifies the action of hexobarbital in rats in vivo. Isopropylphenylimidazole enhances the hydration of cyclohexene oxide and styrene oxide by rat liver preparations when added in vitro; its potency for this effect is considerably greater than that of metyrapone. Isopropylphenylimidazole yields a type II difference spectrum when added to oxidized rat liver microsomes. The double-reciprocal form of the spectral titration curve is linear only at very low microsomal concentrations; under such conditions, a Ks of about 0.5 µM is found. With reduced rat liver microsomes, isopropylphenylimidazole yields two spectral peaks, the amplitude ratio of which is pH-dependent.
Footnotes
- Received June 29, 1973.
- Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics
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