识别细胞色素P450酶参与zotepine的新陈代谢,抗精神病药物,在人类肝脏微粒体。

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金子Shiraga T H, Iwasaki K, Tozuka Z,铃木,要么T

识别细胞色素P450酶参与zotepine的新陈代谢,抗精神病药物,在人类肝脏微粒体。

Xenobiotica。1999年3月29日(3):217 - 29。doi: 10.1080 / 004982599238623。

PubMed ID

10219963 (在PubMed

]

文摘

1。研究用人类肝微粒体和重组人细胞色素P450 (P450)酶和flavin-containing单氧酶(FMO)进行识别酶负责zotepine代谢物在人的形成。2。人类的肝脏微粒体产生四个代谢物和一个试探性的重要性顺序是:norzotepine, 3-hydroxyzotepine, zotepine S-oxide 2-hydroxyzotepine。Zotepine N-oxide也被检测到,但是它不能量化。3所示。主要代谢物的生成率,norzotepine, zotepine S-oxide (20 microM)的底物浓度有显著相关的睾丸激素6 beta-hydroxylase活动和CYP3A4内容12种不同的人类肝脏微粒体样本。抑制研究P450酶选择性抑制剂和anti-rat CYP3A2 CYP3A4的抗体也表示了主要作用形成norzotepine和zotepine S-oxide。Furafylline和sulphaphenazole抑制去zotepine大约30%。4所示。 Correlation and inhibition data for the 2- and 3-hydroxylation of zotepine were consistent with the predominant role of CYP1A2 and 2D6 in the formation of these metabolites, respectively. 5. Recombinant CYP1A1, 1A2, 2B6, 2C19, 3A4 and 3A5 efficiently catalysed N-demethylation of zotepine. CYP1A1, 1A2, 2B6 and 3A4 were also active for S-oxidation. CYP1A2 and 2D6*1-Val374 efficiently produced 2-hydroxyzotepine and 3-hydroxyzotepine, respectively. Recombinant human FMO3 did not catalyse zotepine S-oxidation. 6. These results suggest that both the N-demethylation and S-oxidation of zotepine are mediated mainly by CYP3A4, and that CYP1A2 and 2D6 play an important role in the 2- and 3-hydroxylation of zotepine, respectively.

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药物酶

药物	酶	类	生物	药理作用	行动
Zotepine	细胞色素P450 1 a2	蛋白质	人类	没有	底物	细节