Sullivan Laura C, Clarke William P, Berg Kelly A
Department of Pharmacology - MS 7764, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Curr Pharm Des. 2015;21(26):3732-8. doi: 10.2174/1381612821666150605111236.
It is now well accepted that receptors can regulate cellular signaling pathways in the absence of a stimulating ligand, and inverse agonists can reduce this ligand-independent or "constitutive" receptor activity. Both the serotonin 5-HT2A and 5-HT2C receptors have demonstrated constitutive receptor activity in vitro and in vivo. Each has been identified as a target for treatment of schizophrenia. Further, most, if not all, atypical antipsychotic drugs have inverse agonist properties at both 5-HT2A and 5-HT2C receptors. This paper describes our current knowledge of inverse agonism of atypical antipsychotics at 5-HT2A/2C receptor subtypes in vitro and in vivo. Exploiting inverse agonist properties of APDs may provide new avenues for drug development.
现在人们普遍认为，受体在没有刺激配体的情况下也能调节细胞信号通路，反向激动剂可以降低这种不依赖配体或“组成性”的受体活性。血清素5-HT2A和5-HT2C受体在体外和体内均已表现出组成性受体活性。它们各自都已被确定为治疗精神分裂症的靶点。此外，大多数（如果不是全部的话）非典型抗精神病药物在5-HT2A和5-HT2C受体上都具有反向激动剂特性。本文描述了我们目前对非典型抗精神病药物在体外和体内对5-HT2A/2C受体亚型的反向激动作用的认识。利用非典型抗精神病药物的反向激动剂特性可能为药物开发提供新途径。
