Serotonergic Mechanisms as Targets for Existing and Novel Antipsychotics
Serotonergic Mechanisms as Targets for Existing and Novel Antipsychotics
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DOI：
10.1007/978-3-642-25761-2_4
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发表时间：
2012-01-01
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影响因子：
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通讯作者：
Meltzer, Herbert Y.
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文献类型：
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作者：
Meltzer, Herbert Y.
多种5-羟色胺（5-HT）受体，特别是5-HT 2A、5-HT 1A、5-HT 6、5-HT 7和5-HT 2C，已被假定有助于非典型抗精神病药物（APD）的作用机制，即，与更可能引起锥体外系副作用（EPS）的典型APD相比，APDs在临床最佳剂量下引起较少的EPS。这一优势，很少有争议，使这些药物的首选治疗精神分裂症和其他适应症的APDs。这些5-HT受体作为新型多受体或独立APD的组分仍然令人感兴趣，并有可能修复精神分裂症的认知缺陷。几乎所有目前可用的非典型APD都是5-HT 2A受体反向激动剂，以及多巴胺（DA）D-2受体拮抗剂或部分激动剂。氨磺必利是一种特殊的非典型APD，具有5-HT 7拮抗作用，以补充其DA D-2/3拮抗作用。一些非典型APD也是5-HT 1A部分激动剂、5-HT 6或5-HT 7拮抗剂，或上述的一些组合。已发现5-HT 2C拮抗作用导致一些非典型APD的代谢副作用，而5-HT 2C激动剂具有作为独立APD和/或认知增强剂的潜力。这篇综述将提供最新的临床前和临床证据的作用，这五个5-HT受体在目前的APD的行动和新的精神药物的开发。
A variety of serotonin (5-HT) receptors, especially 5-HT2A, 5-HT1A, 5-HT6, 5-HT7, and 5-HT2C, have been postulated to contribute to the mechanism of action of atypical antipsychotic drugs (APDs), i.e., APDs which cause fewer extrapyramidal side effects (EPS) at clinically optimal doses, in contrast with typical APDs, which are more likely to cause EPS. This advantage, rarely disputed, has made such drugs the preferred treatment for schizophrenia and other indications for APDs. These 5-HT receptors are still of interest as components of novel multireceptor or stand-alone APDs, and potentially to remediate cognitive deficits in schizophrenia. Almost all currently available atypical APDs are 5-HT2A receptor inverse agonists, as well as dopamine (DA) D-2 receptor antagonists or partial agonists. Amisulpride, an exceptional atypical APD, has 5-HT7 antagonism to complement its DA D-2/3 antagonism. Some atypical APDs are also 5-HT1A partial agonists, 5-HT6, or 5-HT7 antagonists, or some combination of the above. 5-HT2C antagonism has been found to contribute to the metabolic side effects of some atypical APDs, whereas 5-HT2C agonists have potential as stand-alone APDs and/or cognitive enhancers. This review will provide an update of current preclinical and clinical evidence for the role of these five 5-HT receptors in the actions of current APDs and for the development of novel psychotropic drugs.