摘要
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
The test of human liver microsome incubation with melatonin (MT), CYP450 1A2 specific inhibitory method, high performance liquid chromatography (HPLC) and electrochemical detection (ED) device were used. The results showed: (1) Fluvoxamine had an inhibitory effect on MT biotransformation similar to that of Furaphylline. Fluvoxamine had strong effects on 6 hydroxylation and O Demethylation with the Ki being 0 024 μmol/L and 0 055 μmol/L ( n =3) respectively. (2) The IC 50 at the concentrations (1 μmol/L or 10 μmol/L) of MT was 0 038 μmol/L or 0 045 μmol/L for 6 hydroxylation and 0 045 μmol/L or 0.048 μmol/L ( n =3) for O Demethylation, respectively. (3) Fluvoxamine and other selective serotonin re uptake inhibitors (SSRIs) were studied for their ability to inhibit human liver cytochrome p450 isoenzyme for MT metabolite. The results indicated that only paroxetin had partial inhibitory effect on p450 isoenzyme.
出处
《同济医科大学学报》
CSCD
2000年第3期202-206,共5页
Acta Universitatis Medicinae Tongji
