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M/M 受体作为精神分裂症潜在治疗方法的研究综述

M/M receptors as potential therapeutic treatments for schizophrenia: A comprehensive study.

机构信息

School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.

School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China..

出版信息

Bioorg Med Chem. 2024 May 1;105:117728. doi: 10.1016/j.bmc.2024.117728. Epub 2024 Apr 16.

Abstract

Muscarinic acetylcholine receptors (mAChRs) play a significant role in the pathophysiology of schizophrenia. Although activating mAChRs holds potential in addressing the full range of schizophrenia symptoms, clinical application of many non-selective mAChR agonists in cognitive deficits, positive and negative symptoms is hindered by peripheral side effects (gastrointestinal disturbances and cardiovascular effects) and dosage restrictions. Ligands binding to the allosteric sites of mAChRs, particularly the M1 and M4 subtypes, demonstrate activity in improving cognitive function and amelioration of positive and negative symptoms associated with schizophrenia, enhancing our understanding of schizophrenia. The article aims to critically examine current design concepts and clinical advancements in synthesizing and designing small molecules targeting M1/M4, providing theoretical insights and empirical support for future research in this field.

摘要

毒蕈碱型乙酰胆碱受体(mAChRs)在精神分裂症的病理生理学中发挥着重要作用。虽然激活 mAChRs 有可能解决精神分裂症的所有症状,但许多非选择性 mAChR 激动剂在认知缺陷、阳性和阴性症状方面的临床应用受到外周副作用(胃肠道紊乱和心血管效应)和剂量限制的阻碍。与 mAChRs 的变构位点结合的配体,特别是 M1 和 M4 亚型,在改善认知功能和改善与精神分裂症相关的阳性和阴性症状方面表现出活性,这增强了我们对精神分裂症的理解。本文旨在批判性地检查目前设计概念和临床进展,以合成和设计针对 M1/M4 的小分子,为该领域的未来研究提供理论见解和经验支持。

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