Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes.
Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes.
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选择性单胺 B 型抑制剂盐酸司来吉兰在人肝微粒体中的代谢。
DOI：
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发表时间：
2002
影响因子：
2.1
通讯作者：
Y. Funae
中科院分区：
文献类型：
--
作者：
Takahiro Kamada;T. Chow;T. Hiroi;S. Imaoka;K. Morimoto;H. Ohde;Y. Funae
研究了细胞色素P-450（CYP）亚型在司来吉兰代谢中的参与。使用在人淋巴母细胞中表达的重组CYP 2B 6亚型的实验表明，CYP 2B 6是参与司来吉兰代谢的主要CYP 2B 6亚型。CYP 1A 2和CYP 3A 4也参与司来吉兰的代谢，但其催化活性远低于CYP 2B 6。与CYP 3A 4和CYP 1A 2相比，CYP 2B 6对司来吉兰的N-去丙基化（K（m）=21.4 microM）和N-去甲基化（K（m）=25.2 microM）具有更高的亲和力。在使用混合人肝微粒体进行的免疫抑制研究中，司来吉兰N-去丙磷酸化活性受到抗CYP 2B和抗CYP 3A抗体的最强抑制，而司来吉兰N-去甲基化活性受到抗CYP 2B抗体的最强抑制。在富含CYP 2B 6的人肝微粒体中，抗CYP 2B抗体对这两种活性的抑制作用最强。司来吉兰抑制CYP 2B 6介导的（S）-美芬妥英N-去甲基化活性和CYP 2C 19介导的（S）-美芬妥英4 '-羟基化活性。这些结果表明，应注意与CYP 2B 6和CYP 2C 19相关的药物相互作用。总之，CYP 2B 6参与司来吉兰的代谢，但其贡献程度因其在人肝脏中的表达水平而异。
The participation of cytochrome P-450 (CYP) isoforms in the metabolism of selegiline was investigated. Experiments using recombinant CYP isoforms expressed in human lymphoblastoid cells showed CYP2B6 to be the major CYP isoform involved with the metabolism of selegiline. CYP1A2 and CYP3A4 also contributed to the metabolism of selegiline but their catalytic activities were much less than that of CYP2B6. CYP2B6 had a higher affinity for both N-depropagylation (K(m)=21.4 microM) and N-demethylation (K(m)=25.2 microM) of selegiline than CYP3A4 and CYP1A2. In immunoinhibition studies using mixed human hepatic microsomes, selegiline N-depropagylation activity was most strongly inhibited by anti-CYP2B and anti-CYP3A antibodies, while selegiline N-demethylation activity was most inhibited by anti-CYP2B antibody. In CYP2B6-rich human hepatic microsomes, anti-CYP2B antibody had the strongest inhibitory effects on both activities. Selegiline inhibited CYP2B6-mediated (S)-mephenytoin N-demethylation activity and CYP2C19-mediated (S)-mephenytoin 4'-hydroxylation activity. These findings suggest that attention should be paid to the drug-drug interaction associated with CYP2B6 and CYP2C19. In conclusion, CYP2B6 participates in the metabolism of selegiline but the degree of its contribution varies with the level of its expression in human liver.
布呋洛尔在人肝微粒体中被细胞色素 P450 2D6 和 1A2 酶羟化。
影响因子：
3.6
作者：
Yamazaki,H;Guo,Z;Persmark,M;Mimura,M;Inoue,K;Guengerich,FP;Shimada,T
通讯作者：
Shimada,T
影响因子：
3.9
作者：
CHANG, TKH;GONZALEZ, FJ;WAXMAN, DJ
通讯作者：
WAXMAN, DJ
丙炔苯丙胺对早期帕金森病残疾进展的影响。
DOI：
10.1056/nejm198911163212004
发表时间：
1989
期刊：
The New England journal of medicine
影响因子：
--
作者：
ParkinsonStudyGroup
通讯作者：
ParkinsonStudyGroup