司立吉林是一个系统,即钝化剂在人类和小鼠体内CYP2A6基因表现抑制尼古丁代谢。

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Siu EC,廷代尔射频

司立吉林是一个系统,即钝化剂在人类和小鼠体内CYP2A6基因表现抑制尼古丁代谢。

J Exp其他杂志》2008年3月,324 (3):992 - 9。Epub 2007年12月7日。

PubMed ID

18065502 (在PubMed

]

文摘

司立吉林(l-deprenyl)是临床治疗试验中作为一个潜在的戒烟药物。我们调查了影响司立吉林及其代谢物的尼古丁代谢。在老鼠中,司立吉林是一个尼古丁代谢的有效抑制剂在肝微粒体和cDNA-expressed CYP2A5;司立吉林代谢物desmethylselegiline, l-methamphetamine l-amphetamine,也抑制尼古丁代谢。预处理和司立吉林desmethylselegiline增加抑制微粒体(IC(50))的3.3和6.1倍,分别。在小鼠体内,增加AUC司立吉林(90.7 + / - 5.8和57.4 + / - 5.3 ng / h /毫升,p < 0.05),减少间隙(4.6 + / - 0.4和7.3 + / - 0.3 ml / min, p < 0.05),消除半衰期增加(12.5 + / - 6.3和6.6 + / - 1.4分钟,尼古丁的p < 0.05)。在体外,司立吉林是一个人类尼古丁代谢的有效抑制剂肝微粒体和cDNA-expressed体内CYP2A6基因表现;desmethylselegiline l-amphetamine也抑制尼古丁代谢。司立吉林预孵化抑制增加微粒体(3.7倍)和体内CYP2A6基因表现(14.8倍);4.2 K (i)体内CYP2A6基因表现为妈妈。 Selegiline dose- and time-dependently inhibited nicotine metabolism by CYP2A6 (K(i) = 15.6 +/- 2.7 muM; k(inact) = 0.34 +/- 0.04 min(-1)), and the inhibition was irreversible in the presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6. Thus, inhibition of mouse nicotine metabolism by selegiline was competitive in vitro and significantly increased plasma nicotine in vivo. In humans, where selegiline is both a competitive and mechanism-based inhibitor, it is likely to have even greater effects on in vivo nicotine metabolism. Our findings suggest that an additional potential mechanism of selegiline in smoking cessation is through inhibition of nicotine metabolism.

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
安非他命	细胞色素P450 2 a6	蛋白质	人类	未知的	抑制剂	细节
司立吉林	细胞色素P450 2 a6	蛋白质	人类	未知的	底物 抑制剂	细节