Dopaminergic receptor antagonism is a crucial component of all licensed treatments for psychosis, and dopamine dysfunction has been central to pathophysiological models of psychotic symptoms. Some clinical trials, however, indicate that drugs that act through muscarinic receptor agonism can also be effective in treating psychosis, potentially implicating muscarinic abnormalities in the pathophysiology of psychosis. Here, we discuss understanding of the central muscarinic system, and we examine preclinical, behavioural, post-mortem, and neuroimaging evidence for its involvement in psychosis. We then consider how altered muscarinic signalling could contribute to the genesis and maintenance of psychotic symptoms, and we review the clinical evidence for muscarinic agents as treatments. Finally, we discuss future research that could clarify the relationship between the muscarinic system and psychotic symptoms.

中文翻译：

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作为毒蕈碱信号传导障碍的精神病：精神病理学和药理学


多巴胺能受体拮抗作用是所有获得许可的精神病治疗的重要组成部分，多巴胺功能障碍一直是精神病症状病理生理学模型的核心。然而，一些临床试验表明，通过毒蕈碱受体激动作用的药物也可以有效治疗精神病，这可能表明精神病病理生理学中的毒蕈碱异常。在这里，我们讨论对中枢毒蕈碱系统的理解，并检查其与精神病有关的临床前、行为、尸检和神经影像学证据。然后，我们考虑毒蕈碱信号的改变如何促进精神病症状的发生和维持，并回顾毒蕈碱药物作为治疗方法的临床证据。最后，我们讨论了未来的研究，这些研究可以阐明毒蕈碱系统与精神病症状之间的关系。