The metabolism of 4-substituted N-ethyl-N-methylanilines. III. Effect of various potential inhibitors, activators and inducers on alpha-C- and N-oxidation

Abstract

The alpha-C-oxidation of N-ethyl-N-methylaniline and of the 4-chloro and 4-methyl derivatives was inhibited by SKF-525A, DPEA, carbon monoxide and cyanide and induced by phenobarbitone but not by 3-methylcholanthrene pretreatment. The N-oxidation of these tertiary anilines was not influenced by SKF-525A, carbon monoxide or cyanide, nor by phenobarbitone or 3-methylcholanthrene pretreatment. The N-oxidase was activated by DPEA and n-octylamine and inhibited by 1-naphthylthiourea. The evidence indicates that metabolic alpha-C-oxidation of these substrates is mediated by a cytochrome P-450-dependent pathway whilst N-oxidation is mediated by a flavo-protein amine oxidase.