单胺转运蛋白与单胺重摄取抑制剂研究进展

5-羟色胺转运蛋白(serotonin transporter,SERT)和去甲肾上腺素转运蛋白(norepinephrine transporter,NET)是单胺类神经递质转运体,其功能是将释放到突触间隙的5-羟色胺(serotonin,5-HT)和去甲肾上腺素(norepinephrine,NE)分别转运入突触前神经细胞,以终止相应的突触信号传递。SERT、NET抑制剂可阻断5-HT和NE的重摄取,提高突触间隙单胺递质水平,从而发挥抗抑郁效应。SERT、NET作为主流抗抑郁药物的作用靶标,了解其分布与功能、分子结构和活性调节因素,以及单胺重摄取抑制剂的作用机制对抗抑郁药物研发及应用具有重要意义。

Research progress in monoamine transporters and monoamine transmitter reuptake inhibitors

Presynaptic membrane serotonin transporters(SERT) and norepinephrine transporter(NET),which are important neurotransmitter transporters,are responsible for reuptake of released serotonin(5-HT) and norepinephrine(NE),respectively.The major function of these transporters is to terminate monoamine transmission by mediating uptake of neurotransmitters from extracellular space into neurons and glial cells.Drugs that inhibit the activity of monoamine transporters produce increased neurotransmitter levels in the synaptic cleft,leading to their therapeutic use in depression.As SERT and NET are pharmacological targets for most antidepressants,understanding about the molecular pharmacology of these transporters,including their localization and function,molecular structure and regulation,as well as drug binding sites and mechanism of action,is important to new antidepressant development.