1. The effects of various potential inhibitors, activators and inducers on the N-oxidation of isomeric aromatic diazines (pyrazine, pyrimidine and pyridazine) by rabbit liver microsomes have been studied. 2. 2,4-Dichloro-6-phenylphenoxyethylamine (DPEA), SKF 525-A and N-octylamine decreased N-oxide formation at 10(-4) M concentrations. 3. Methimazole and carbon monoxide inhibited the N-oxidation of all three substrates studied. 4. The inhibitory effects were generally exaggerated when hepatic microsomal preparations from phenobarbitone-pretreated animals were used as enzyme source. 5. When phenobarbitone or pyridine were used as inducing agents, the N-oxidation of isomeric aromatic diazines showed considerable induction, whereas beta-naphthoflavone and Arochlor 1254 pretreatment had much weaker effects. 6. It is suggested that P4502E1 and/or 2B are the major subfamilies of P450 involved in the N-oxidation of isomeric diazines.

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