PDF(Pubmed)
Abstract：
Pre-clinical models, postmortem and neuroimaging studies all support a role for muscarinic receptors in the molecular pathology of schizophrenia. From these data it was proposed that activation of the muscarinic M1 and/or M4 receptor would reduce the severity of the symptoms of schizophrenia. This hypothesis is now supported by results from two clinical trials which indicate that activating central muscarinic M1 and M4 receptors can reduce the severity of positive, negative and cognitive symptoms of the disorder. This review will provide an update on a growing body of evidence that argues the muscarinic M1 and M4 receptors have critical roles in CNS functions that are dysregulated by the pathophysiology of schizophrenia. This realization has been made possible, in part, by the growing ability to visualize and quantify muscarinic M1 and M4 receptors in the human CNS using molecular neuroimaging. We will discuss how these advances have provided evidence to support the notion that there is a sub-group of patients within the syndrome of schizophrenia that have a unique molecular pathology driven by a marked loss of muscarinic M1 receptors. This review is timely, as drugs targeting muscarinic receptors approach clinical use for the treatment of schizophrenia and here we outline the background biology that supported development of such drugs to treat the disorder.
摘要：
临床前模型,验尸和神经影像学研究都支持毒蕈碱受体在精神分裂症分子病理学中的作用。根据这些数据,提出毒蕈碱M1和/或M4受体的激活将降低精神分裂症症状的严重程度。这一假设现在得到了两项临床试验的结果的支持，这表明激活中枢毒蕈碱M1和M4受体可以降低阳性的严重程度，该疾病的阴性和认知症状。这篇评论将提供越来越多的证据的更新，这些证据认为毒蕈碱M1和M4受体在精神分裂症的病理生理学失调的中枢神经系统功能中具有关键作用。这种认识已经成为可能，在某种程度上,通过使用分子神经成像技术来可视化和量化人类CNS中毒蕈碱M1和M4受体的能力。我们将讨论这些进展如何提供证据来支持以下观点：精神分裂症综合征中有一个亚组患者具有由毒蕈碱M1受体明显丧失驱动的独特分子病理学。这次审查是及时的,作为靶向毒蕈碱受体的药物接近临床用于治疗精神分裂症，在这里我们概述了支持开发此类药物治疗精神分裂症的背景生物学。
