Effects of ozagrel (OKY-046), a thromboxane synthase inhibitor, on oxidative drug-metabolizing enzymes in mouse hepatic microsomes.
Effects of ozagrel (OKY-046), a thromboxane synthase inhibitor, on oxidative drug-metabolizing enzymes in mouse hepatic microsomes.
复制标题
血栓素合成酶抑制剂奥扎格雷 (OKY-046) 对小鼠肝微粒体中氧化药物代谢酶的影响。
DOI：
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发表时间：
1988
期刊：
影响因子：
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通讯作者：
H. Shimakawa
中科院分区：
文献类型：
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作者：
K. Morita;T. Ono;H. Shimakawa
研究了咪唑衍生物奥扎格雷尔（ozagrel， OZA）对小鼠肝微粒体单加氧酶系统的抑制作用。单次给药100 mg/kg OZA可显著延长戊巴比妥睡眠时间，OZA延长睡眠时间的效力与西咪替丁相似。在体外，OZA对肝微粒体氨基吡啶n -去甲基化酶、苯胺羟化酶和睾酮6 β -和7 α -羟化酶活性的抑制常数（Ki）为0.19 ~ 3.72 mM，其对这些酶活性的抑制作用与西咪替丁相似，而对睾酮16 α -羟化酶活性无抑制作用。分光光度法研究表明，OZA的咪唑部分与细胞色素P-450结合，对还原性烟酰胺腺嘌呤二核苷酸磷酸细胞色素c还原酶活性影响不大。这些结果表明OZA是一些细胞色素p -450介导的肝微粒体药物代谢的抑制剂。
The inhibitory effects of ozagrel (OZA), an imidazole derivative and a specific thromboxane synthase inhibitor, on a monooxygenase system in mouse hepatic microsomes were studied. Pentobarbital sleeping time was significantly prolonged by i.p. administration of a single dose of 100 mg/kg of OZA, and the potency of OZA for the prolongation of sleeping time was similar to that of cimetidine. In vitro, OZA inhibited aminopyrine N-demethylase, aniline hydroxylase and testosterone 6 beta- and 7 alpha-hydroxylase activities in hepatic microsomes with inhibition constants (Ki) of 0.19-3.72 mM. The potency and the mode of inhibition of OZA for these enzyme activities were similar to those of cimetidine, while no inhibitory effect of OZA on testosterone 16 alpha-hydroxylase activity was found. A spectrophotometric study revealed that the imidazole moiety of OZA binds to cytochrome P-450 and has little effect on reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity. These results indicated that OZA is an inhibitor of some cytochrome P-450-mediated drug metabolism in hepatic microsomes.