丙咪嗪的代谢的主要途径是由细胞色素p - 450催化1 a2和p - 450 3 a4在人类肝脏。

文章的细节

引用

复制到剪贴板

D·阿祖莱莱莫恩,Gautier JC, Kiffel L, C贝洛克,Guengerich FP, Maurel P,博纳P, Leroux JP

丙咪嗪的代谢的主要途径是由细胞色素p - 450催化1 a2和p - 450 3 a4在人类肝脏。

43摩尔杂志。1993;(5):827 - 32。

PubMed ID

8502233 (在PubMed

]

文摘

丙咪嗪的代谢人类肝脏微粒体检查使用五个策略的组合。人肝微粒体产生N-desmethylimipramine (84%)、2-hydroxyimipramine(10%),和10-hydroxyimipramine (6%)。预培养的人类肝细胞在文化beta-naphthoflavone和大环内酯类专门诱导形成desmethylimpramine (552%, p < 0.05, 234%, p < 0.003)。率之间的相关性得到丙咪嗪脱甲基作用和细胞色素p - 450 (p - 450) 1 a2 (r = 0.88, p < 0.001)和3 p - 450 (r = 0.80, p < 0.02)浓度在人类肝脏微粒体准备来自13个不同的主题。反- p - 450 1 a2和反- 3 p - 450抗体有选择地去甲基化抑制(分别为80%和60%)。去完全抑制当anti-1A2 anti-3A同时被添加。与人类微粒体动力学研究证实两种不同的贡献去甲基酶。1 a2的公里是类似于人类的高亲和力公里肝微粒体,而3公里的类似于低亲和力公里在人类肝脏微粒体。p - 450 1 a2显然是更有效的比3 a4(更低的公里和更高的Vmax),但表达的浓度要低得多。人类的p - 450 1 a2和3 a4 desmethylimipramine产生的酵母高效表达。 These results suggest that P-450 1A2 and P-450 3A4 are the major enzymes involved in imipramine N-demethylation in human hepatic microsomes. Similar experiments were conducted using P-450 2D6, and they confirmed that P-450 2D6 catalyzes imipramine 2-hydroxylation. Interindividual variations in 3A4 hepatic content may explain the large variations in imipramine blood levels observed after uniform dosages and thus may explain the variations in clinical efficacy. Caution might be advised in the clinical use of tricyclic antidepressants when drugs are also administered that induce or inhibit P-450s 3A4 and 1A2.

beplay体育安全吗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
丙咪嗪	细胞色素P450 1 a2	蛋白质	人类	未知的	底物 抑制剂	细节