Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes
Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes
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DOI：
10.1016/j.bcp.2006.01.015
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发表时间：
2006-04-28
影响因子：
5.8
通讯作者：
Hanioka, N
中科院分区：
文献类型：
--
作者：
Narimatsu, S;Yonemoto, R;Hanioka, N
使用人肝微粒体组分、重组 CYP 酶和合成 5-MeO-DIPT 代谢物对（S-甲氧基-N,N-二异丙基色胺、5-MeO-DIPT、Foxy）的氧化代谢进行体外定量研究。在混合的人肝微粒体中，5-MeO-DIPT 主要被氧化为 O-去甲基化 (5-OH-DIPT) 和 N-去异丙基化 (S-MeO-IPT) 代谢物。在动力学研究中，5-MeO-DIPT O-脱甲基化表现出单相动力学，而其 N-脱异丙基化表现出三相动力学。在酵母或昆虫细胞中表达的六种重组CYP酶（CYP1A2、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4）中，只有CYP2D6表现出5-MeO-DIPT O-脱甲基酶活性，而CYP1A2、CYP2C8、CYP2C9、CYP2C19和CYP3A4显示 5-MeO-DIPT N-脱异丙酶活性。 CYP2D6 的表观 K, 值与 5-MeO-D1PT O-去甲基化的表观 K, 值接近，其他 CYP 酶的 K-m 值分别与人肝脏中 N-去异丙基化的低 Km (CYP2C19)、中 K-m (CYP1A2、CYP2C8 和 CYP3A4) 和高 K-m 相 (CYP2C9) 相似。微粒体。在抑制研究中，CYP2D6抑制剂奎尼丁（1μM）在底物浓度为10μM时几乎完全抑制人肝微粒体5-MeO-DIPT O-去甲基化。
In vitro quantitative studies of the oxidative metabolism of (S-methoxy-N,N-diisopropyl-tryptamine, 5-MeO-DIPT, Foxy) were performed using human liver microsomal fractions and recombinant CYP enzymes and synthetic 5-MeO-DIPT metabolites. 5-MeO-DIPT was mainly oxidized to O-demethylated (5-OH-DIPT) and N-deisopropylated (S-MeO-IPT) metabolites in pooled human liver microsomes. In kinetic studies, 5-MeO-DIPT O-demethylation showed monophasic kinetics, whereas its N-deisopropylation showed triphasic kinetics. Among six recombinant CYP enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) expressed in yeast or insect cells, only CYP2D6 exhibited 5-MeO-DIPT O-demethylase activity, while CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4 showed 5-MeO-DIPT N-deisopropylase activities. The apparent K, value of CYP2D6 was close to that for 5-MeO-D1PT O-demethylation, and the K-m values of other CYP enzymes were similar to those of the low-Km (CYP2C19), intermediate-K-m (CYP1A2, CYP2C8 and CYP3A4) and high-K-m phases (CYP2C9), respectively, for N-deisopropylation in human liver microsomes. in inhibition studies, quinidine (1 mu M), an inhibitor of CYP2D6, almost completely inhibited human liver microsomal 5-MeO-DIPT O-demethylation at a substrate concentration of 10 mu M.