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标题：In Vitro Confirmation of Selegiline N-Oxidation by Flavin-Containing Monooxygenase in Rat Microsome Using LC-ESI MS
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作者：Hiroe Tsutsumi ; Munehiro Katagi ; Mayumi Nishikawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：10
页码：1572-1575
DOI：10.1248/bpb.27.1572
出版社：The Pharmaceutical Society of Japan
摘要：In order to investigate the conversion of selegiline (SG), a drug used in the treatment of Parkinson's disease, to selegiline N -oxide (SGO) as a major metabolic pathway for SG, rat liver microsomal incubations were carried out in vitro in the presence of NADPH. SG was transformed into SGO in vitro as described in our previous human in vivo experiment. In the kinetic studies, the V _max/ K _m value of the N -oxidation at pH 8 was found to be approximately four times greater than that at pH 7.4. The N -oxidation was also found to be inhibited by methimazole, an inhibitor of the flavin-containing monooxigenase (FMO) rather than by SKF 525A, an inhibitor of cytochrome P450s, and stimulated approximately two times by n -octylamine, an stimulator of FMO. Moreover, the N -oxidation activity remained almost unchanged in the presence of NADPH even after heating at 50 °C for a few minutes. The present data demonstrate that the N -oxidation of SG to SGO is principally mediated by FMO.
关键词：selegiline;N-oxidation;flavin-containing monooxygenase (FMO)