形成胍诺沙苄胍那苄在人类肝脏。一个新的代谢CYP1A2的标志。

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克莱门特B, Demesmaeker M

形成胍诺沙苄胍那苄在人类肝脏。一个新的代谢CYP1A2的标志。

药物金属底座Dispos。1997年11月,25 (11):1266 - 71。

PubMed ID

9351903 (在PubMed

]

文摘

的体外N-hydroxylation胍那苄以及相应的胍诺沙苄N-dehydroxylation以前生物转化研究中发现了微粒体分数不同的物种包括人类肝微粒体。此外,胍那苄被发现催化的N-hydroxylation丰富细胞色素P450 (P450)分数在重组系统。很强的相关性之间7-ethoxyresorufin O-deethylation (r = 0。96;去甲基化p < 0.001)、咖啡因(r = 0.92;p < 0.001),分别和胍那苄N-hydroxylation活动是10人肝微粒体中演示的准备。研究微粒体从人类B-lymphoblastoid细胞系表达人细胞色素P450酶证明CYP1A2是主要负责同工酶代谢途径。此外,P450酶同功酶没有任何可探测的转化率。面前的反应是抑制CYP1A2的抑制剂alpha-naphthoflavone (7, 8-benzoflavone)和furafylline。的N-reduction胍诺沙苄胍那苄展品的显著相关性benzamidoxime N-reduction孵化后10人肝微粒体准备(r = 0.97; p < 0.001). The formation of benzamidine from benzamidoxime was described previously to be catalyzed by the benzamidoxime reductase. These results suggest that the guanabenz N-hydroxylation is mediated via CYP1A2, whereas the corresponding guanoxabenz N-reduction is catalyzed by an enzyme system composed of cytochrome b5, NADH cytochrome b5-reductase, and benzamidoxime reductase. The high affinity of guanabenz to CYP1A2 and the distinct selectivity of this P450 isozyme toward guanabenz confirms the in vitro guanabenz N-hydroxylation to be a suitable metabolic marker for CYP1A2 in biotransformation studies.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
胍那苄	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节