Biotransformation of azapetine to oxazapetine in rat and rabbit liver fractions.
The biotransformation of azapetine (I) to a lactam metabolite, oxazapetine (II), has been investigated in rat and rabbit hepatic subcellular fractions. In the presence of NADPH, II was produced from I in incubation mixtures containing 9000 g supernatant fraction or combined microsomes and cytosol, but not in mixtures containing microsomes or cytosol alone. Production of II was also observed when dehydrozapetine (III) was incubated with rabbit 9000 g supernatant fraction or cytosol. In washed rabbit microsomes II was not produced from III, but I was converted to III in the presence of NADPH. These results suggested that the biotransformation is initiated by microsomal enzymatic oxidation of I to III, followed by further oxidation of III to II by a soluble enzyme.
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003984:Dibenzazepines / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D003984:Dibenzazepines; D009249:NADP