EFFECT OF VARIOUS POTENTIAL INHIBITORS, ACTIVATORS AND INDUCERS ON THE N-OXIDATION OF ISOMERIC AROMATIC DIAZINES IN-VITRO USING RABBIT LIVER MICROSOMAL PREPARATIONS

1. The effects of various potential inhibitors, activators and inducer s on the N-oxidation of isomeric aromatic diazines (pyrazine, pyrimidi ne and pyridazine) by rabbit liver microsomes have been studied. 2. 2, 4-Dichloro-6-phenylphenoxyethylamine (DPEA), SKF 525-A and N-octylamin e decreased N-oxide formation at 10(-4) M concentrations. 3. Methimazo le and carbon monoxide inhibited the N-oxidation of all three substrat es 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 mere us ed as inducing agents, the N-oxidation of isomeric aromatic diazines s howed considerable induction, whereas beta-naphthoflavone and Arochlor 1254 pretreatment had much weaker effects. 6. It is suggested that P4 502E1 and/or 2B are the major subfamilies of P450 involved in the N-ox idation of isomeric diazines.