The metabolism of 4-substituted N-ethyl-N-methylanilines. III. Effect of various potential inhibitors, activators and inducers on alpha-C- and N-oxidation.
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.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology
D000814:Aniline Compounds; D008748:Methylcholanthrene; C010951:N-ethyl-N-methylaniline; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010634:Phenobarbital