A new class of inhibitory cytochrome P-450 complexes formed during metabolism: a comparison with amphetamine and SKF 525-A type complexes

Abstract

During the metabolism of p-chloroaniline, sulfanilamide, 2-methylindoline, and dapsone, complexes with cytochrome P-450 are formed which absorb maximally at 448, 450, 451, and 452 nm, respectively. These complexes are similar to the complexes from amphetamines (456 nm) and SKF 525-A (452 nm) in the conditions for, and rate of their formation, and their inhibition of ethylmorphine N-demethylase activity. Similarly, the formation is mainly a property of phenobarbital-induced cytochrome P-450 and is inhibited by comparable concentrations of metyrapone and 2-O-iodophenoxymethylimidazole. Unlike the complexes from amphetamine and SKF 525-A, those formed from p-chloroaniline, sulfanilamide, 2-methylindoline, and dapsone are unstable in the presence of sodium dithionite.