4种临床常见选择性5-羟色胺再摄取抑制剂对5-羟色胺转运体的抑制作用比较

In Vitro Comparison of Four SSRIs' Inhibitory Effect on Serotonin Transport

目的选择性5-羟色胺(5-HT)再摄取抑制剂(selective serotonin reuptake inhibitors,SSRIs)是目前临床应用最广泛的新型抗抑郁药物。通过考察氟西汀、帕罗西汀、西酞普兰和舍曲林对5-HT转运体(serotonin transporter,SERT)的抑制作用的强弱,为临床选择药物提供实验依据。方法利用大鼠脑突触体和大鼠血小板SERT,通过放射配基实验,观察在SSRIs存在下SERT对[3H]5-HT的摄取变化,获得IC50值,比较氟西汀、帕罗西汀、西酞普兰和舍曲林对SERT抑制作用的强弱。结果大鼠脑组织突触体和血小板SERT体外放射配基结合实验显示,帕罗西汀、氟西汀、西酞普兰和舍曲林对SERT抑制作用的IC50(nmol.L-1)分别为(血小板vs突触体):(1.26vs1.39)、(44.7vs35.5)、(10.5vs16.2)和(6.64vs7.09)。结论4种SSRIs对SERT的抑制作用都很强,IC50在nmol.L-1数量级。抑制作用的强弱依次为帕罗西汀>舍曲林>西酞普兰>氟西汀。

OBJECTIVE To investigate the strength of SSRIs ＇ inhibitory effects on serotonin transporter , SERT and to offerprescription information for clinical therapy. METHODS The activity of SERT in rat synaptosomes and platelets was measured by determining the rate of [ ^3H ] 5-HT accumulation under different concentration of paroxetine, fluoxetine, citalopram and sertraline. The IC50s of these SSRIs were calculated by linear regression. RESULTS The IC50s （ platelet vs synaptosome） of paroxetine, fluoxetine, citalopram and sertraline were 1.26 vs 1.39, 44. 7 vs 35.5, 10. 5 vs 16. 2 and 6.64 vs 7.09, respectively. CONCLUSION These widely used SSRIs have strong inhibitory effect on rat platelet and synaptosome SERT. Paroxetine has the most potent inhibitory effect and fluoxetine is the weakest one.