Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity
Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity
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DOI：
10.1016/s0925-4439(02)00071-6
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发表时间：
2002-05-21
影响因子：
6.2
通讯作者：
Schetinger, MRC
中科院分区：
文献类型：
--
作者：
Müller, TC;Rocha, JBT;Schetinger, MRC
本研究观察了抗抑郁药氟西汀、舍曲林和阿米替林对人血清和红细胞膜胆碱酯酶(乙酰胆碱酯酶和丁基胆碱酯酶)活性的影响。氟西汀和阿米替林的浓度范围为3-60微米，舍曲林的浓度范围为0.3-12微米。在微摩尔浓度范围内，不同类别的抗抑郁药，包括氟西汀、舍曲林(选择性5-羟色胺再摄取抑制剂(SSRIs))和阿米替林(三环抗抑郁药)对人血清胆碱酯酶有抑制作用。抑制作用强于氟西汀的依次为舍曲林和阿米替林，IC50值分别为4.05、9、43和62微米。动力学数据分析表明，所有抗抑郁药的抑制作用本质上是混合的。在微摩尔浓度范围内，舍曲林(60-120um)和阿米替林(60-180um)对人红细胞AChE的抑制作用依次为舍曲林和阿米替林，IC50值分别为80和134um。动力学数据分析表明，所有抗抑郁剂对AChE人红细胞膜(GHOST)的抑制作用具有混合性。舍曲林与胆碱酯酶的相互作用是不稳定的，因为凝胶过滤去除了抑制剂，完全恢复了酶的活性。我们的结果表明，临床上常用的抗抑郁药是人血清和红细胞膜上胆碱酯酶的抑制剂。(C)2002 Elsevier Science B.V.保留所有权利。
This study examines the effect of the antidepressants fluoxetine, sertraline and amitriptyline on cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) activities in human serum and erythrocyte membrane (ghost). The concentrations used range from 3 to 60 muM for fluoxetine and amitriptyline and 0.3 to 12 muM for sertraline. At the micromolar range concentration, different classes of antidepressants, including fluoxetine and sertraline (selective serotonin reuptake inhibitors (SSRIs)) and amitriptyline (tricyclic antidepressant) inhibited human serum cholinesterase. The order of inhibitory potency was sertraline>amitriptylinemuch greater thanfluoxetine and the IC50 values were 4.05, 9,43 and 62 muM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants was mixed in nature. At the micromolar range concentration, sertraline (60-120 muM) and amitriptyline (60 180 muM) inhibited human erythrocyte AChE, The order of inhibitory potency was sertraline>amitriptyline and the IC50 values were 80 and 134 muM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants in AChE human erythrocyte membrane (ghost) was mixed in nature. The interaction of sertraline with the cholinesterase is labile since the removal of inhibitor by gel filtration recovered completely the enzyme activity. Our results demonstrate that the usual clinical antidepressants are inhibitors of the cholinesterases on human serum and erythrocyte membrane. (C) 2002 Elsevier Science B.V. All rights reserved.