新靶点抗精神病药SEP-363856研究进展

Research progress of new target antipsychotic drug-SEP-363856

精神分裂症是一种慢性高致残性精神障碍,其病因和病理机制复杂。既往抗精神病药主要通过作用于多巴胺2型受体发挥疗效,对阴性症状和认知损害症状的疗效欠佳且出现较多的不良反应,严重影响患者的治疗依从性和功能康复。因此,作用于新靶点的抗精神病药的研发显得尤为迫切。SEP-363856是基于表型筛选策略发现的一种不与多巴胺2型受体结合的独特抗精神病药,临床前研究数据表明,SEP-363856的疗效可能与激活痕量胺相关受体1和5-羟色胺1A受体有关,该药的发现有望为精神分裂症患者带来新的治疗选择。本文中简要介绍了SEP-363856的研发历程,包括临床前研究结果及最新的临床试验数据,便于读者了解这一新型抗精神病药。

Schizophrenia is a common chronic disabling mental disorder with complex etiology and pathological mechanism.Over the past 70 years,antipsychotics have primarily acted on D2 receptors,with poor response to negative symptoms and cognitive impairment and more adverse effects,which have significantly affected patient compliance and functional recovery.Therefore,the development of new-targeted antipsychotic drugs is particularly urgent.SEP-363856 is a non-D2-receptor-binding drug for the treatment of schizophrenia which is found by phenotypic screening strategies,and the pharmacological mechanism has not been fully elucidated.Preclinical data suggest that SEP-363856 may active Trace amine associated receptor 1(TAAR1)and 5-HT1A receptors,and the discovery of this drug shed light on new treatment options for schizophrenic.This review provides an introduction of the development of SEP-363856,including preclinical findings and the latest clinical trial data,to help readers understand this new antipsychotic drug.