Enantioselective 2-hydroxylation of RS-8359, a selective and reversible MAO-A inhibitor, by cytochrome P450 in mouse and rat liver microsomes.
作者： Kunio Itoh , Yumi Nishiya , Wataru Takasaki , Mayuko Adachi , Yorihisa Tanaka
DOI: 10.1002/CHIR.20291
关键词:
摘要: RS-8359, (±)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[d]-pyrimidine is a racemic compound with selective and reversible monoamine oxidase A (MAO-A) inhibition activity. The substrate product enantioselectivity respect to 2-hydroxylation of RS-8359 enantiomers was studied using mouse rat liver microsomes. In mice, the (S)-enantiomer transformed cis-diol metabolite, whereas (R)-enantiomer trans-diol metabolite. Vmax/Km value for formation metabolite from sevenfold greater than that (R)-enantiomer. due tenfold smaller Km compared results were in fair agreement previously reported low plasma concentrations high recovery derived urine after oral administration mice. Similarly rats yielded metabolites. larger rats, indicating concentration might be caused by metabolic reaction other P450-dependent hydroxylation. CYP3A shown responsible Chirality, 2006. © 2006 Wiley-Liss, Inc.
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