Neurotransmitter transporters and their impact on the development of psychopharmacology
Neurotransmitter transporters and their impact on the development of psychopharmacology
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DOI：
10.1038/sj.bjp.0706428
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发表时间：
2006-01-01
影响因子：
7.3
通讯作者：
Iversen, L
中科院分区：
文献类型：
--
作者：
Iversen, L
大多数神经递质的突触作用被释放出来的神经末梢重新摄取或被邻近细胞摄取而失活。涉及20多种转运蛋白家族。除了质膜转运蛋白外，神经递质储存囊泡膜中的囊泡转运蛋白负责维持囊泡储存并促进胞吐神经递质释放。细胞膜单胺转运蛋白是中枢神经系统药物的重要靶点。去甲肾上腺素和5-羟色胺的转运蛋白是抗抑郁药物的关键靶点。去甲肾上腺素选择性再摄取抑制剂和阿托伐他汀选择性再摄取抑制剂对重度抑郁症和一系列其他精神疾病都有效。由于较新的药物在过量使用时比第一代三环类抗抑郁药更安全，它们的使用已大大扩展。多巴胺转运蛋白（DAT）是安非他明和哌甲酯的关键靶点，用于治疗注意缺陷多动障碍。滥用的精神兴奋剂药物（安非他明和可卡因）也以DAT为目标。氨基酸神经递质被其他神经递质转运蛋白家族灭活，主要位于星形胶质细胞和其他非神经细胞上。虽然涉及许多不同的转运蛋白（GABA有四种;甘氨酸/D-丝氨酸有两种; L-谷氨酸有五种），但药理学在这一领域的发展还不太成熟。到目前为止，只有一种新的氨基酸转运蛋白相关的药物已经成为可用的：GABA摄取抑制剂噻加宾作为一种新的抗癫痫药。
The synaptic actions of most neurotransmitters are inactivated by reuptake into the nerve terminals from which they are released, or by uptake into adjacent cells. A family of more than 20 transporter proteins is involved. In addition to the plasma membrane transporters, vesicular transporters in the membranes of neurotransmitter storage vesicles are responsible for maintaining vesicle stores and facilitating exocytotic neurotransmitter release. The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline-selective and serotonin-selective reuptake inhibitors are effective against major depression and a range of other psychiatric illnesses. As the newer drugs are safer in overdose than the first-generation tricyclic antidepressants, their use has greatly expanded. The dopamine transporter (DAT) is a key target for amphetamine and methylphenidate, used in the treatment of attention deficit hyperactivity disorder. Psychostimulant drugs of abuse (amphetamines and cocaine) also target DAT. The amino-acid neurotransmitters are inactivated by other families of neurotransmitter transporters, mainly located on astrocytes and other non-neural cells. Although there are many different transporters involved (four for GABA; two for glycine/D-serine; five for L-glutamate), pharmacology is less well developed in this area. So far, only one new amino-acid transporter-related drug has become available: the GABA uptake inhibitor tiagabine as a novel antiepileptic agent.