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采用人肝微粒体温育实验、CYP45 0 1A2特异性抑制法以及 HPL C和电化学分析仪检测的结果表明 :1抗抑郁药 Fluvoxamine(三氟戊肟胺 )对 CYP45 0 1A2具有和 CYP45 0 1A2特异抑制剂 Furaphyllin(呋拉茶碱 )同样的对 MT生物转化的抑制作用 ,并求测其动力学参数。Fluvoxam ine对 MT羟化反应有很强的抑制作用 ,其 Ki=0 .0 2 4μmol/ L;对 MT去甲基反应也是抑制的 ,其 Ki=0 .0 5 5 μmol/ L (n=3)。 2在 MT浓度为 1μmol/ L 和 10 μmol/ L 时 ,在羟化反应中其 IC5 0 分别为 0 .0 38μm ol/ L 和 0 .0 45 μm ol/ L;在去甲基反应中 IC5 0 分别为 0 .0 45 μmol/ L 和 0 .0 48μmol/ L (n=3)。3其它与 Fluvoxamine同属选择 5 -羟色胺再吸收抑制剂类 (SSRIs)中 ,除了 Fluvoxam ine外 ,只有 paroxetin (帕罗西汀 )对 CYP45 0异构酶有部分抑制作用 ,其它 SSRIs均无显著的抑制作用
The results of human liver microsomal incubation test, CYP45 0 1A2 specific inhibition assay and HPL C and electrochemical analyzer showed that 1 anti-depressant Fluvoxamine was specific to CYP45 0 1A2 and CYP45 0 1A2 Inhibitor Furaphyllin (of furilactine) similarly inhibits MT biotransformation and determines its kinetic parameters. Fluvoxamine has a strong inhibitory effect on the hydroxylation of MT. The Ki = 0. 24 μmol / L and the demethylation of MT were also inhibited. Ki = 0. 05 μmol / L (n = 3 ). 2 At IC50 of 1 μmol / L and 10 μmol / L, the IC 50 values were 0.388μmol / L and 0.455μmol / L respectively in the hydroxylation reaction. The IC50 values of the demethylation reaction Were 0 .0 45 μmol / L and 0. 48 μmol / L respectively (n = 3). 3 Other serotonin reuptake inhibitors (SSRIs) of the same serotonin reuptake inhibitors (SSRIs), except for paroxetine (paroxetine), partially inhibited CYP45 isomerase except for Fluvoxamide, with no significant inhibitory effect on other SSRIs