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 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.
Altuntas
T G
TG
Chelsea Department of Pharmacy, University of London, UK.
Gorrod
J W
JW
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002248:Carbon Monoxide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007536:Isomerism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011719:Pyrazines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D011817:Rabbits
D000963:Antimetabolites; D011719:Pyrazines; D011743:Pyrimidines; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System