Schizophrenia is a major mental illness associated with profound disability. Current treatments for schizophrenia (antipsychotics) all have a similar mechanism of action and are primarily dopamine type 2 receptor (D₂R) antagonists. Antipsychotics are not fully effective for the majority of schizophrenia patients, suggesting the need for alternative approaches. The primary focus of this review is to assess the evidence for the role of the serotonin type 2A receptor (5-HT_2AR) in schizophrenia. Topics include an overview of 5-HT_2AR physiology and pathophysiology in schizophrenia, 5-HT_2AR interaction with other neurotransmitter systems, including the glutamatergic system, a review of the 5-HT_2AR/d-lysergic acid diethylamide (LSD) model of schizophrenia, a contrast of the 5-HT_2AR and glutamatergic models of schizophrenia, and finally, a review of Food and Drug Administration (FDA)-approved and investigational 5-HT_2AR-modulating compounds. Recent studies with lumeteperone, pimavanserin, and roluperidone are highlighted.

精神分裂症是一种与严重残疾相关的主要精神疾病。目前对精神分裂症（抗精神病药）的治疗都具有相似的作用机制，主要是多巴胺 2 型受体 (D ₂ R) 拮抗剂。抗精神病药对大多数精神分裂症患者并不完全有效，这表明需要其他替代方法。本综述的主要重点是评估血清素 2A 型受体 (5-HT _2A R) 在精神分裂症中的作用的证据。主题包括精神分裂症中 5-HT _2A R 生理学和病理生理学的概述、5-HT _2A R 与其他神经递质系统（包括谷氨酸能系统）的相互作用、对 5-HT _2A的回顾精神分裂症的 R/d-麦角酸二乙胺 (LSD) 模型，5-HT _2A R 和精神分裂症的谷氨酸能模型的对比，最后，食品和药物管理局 (FDA) 批准和研究的 5-HT _2A的审查R-调节化合物。重点介绍了最近对卢美特酮、匹马万色林和鲁哌啶酮的研究。