Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, United States; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, United States.
Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, United States; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, United States.
Behav Brain Res. 2021 May 7;405:113201. doi: 10.1016/j.bbr.2021.113201. Epub 2021 Feb 26.
Schizophrenia is a severe neuropsychiatric disorder characterized by a diverse range of symptoms that can have profound impacts on the lives of patients. Currently available antipsychotics target dopamine receptors, and while they are useful for ameliorating the positive symptoms of the disorder, this approach often does not significantly improve negative and cognitive symptoms. Excitingly, preclinical and clinical research suggests that targeting specific muscarinic acetylcholine receptor subtypes could provide more comprehensive symptomatic relief with the potential to ameliorate numerous symptom domains. Mechanistic studies reveal that M1, M4, and M5 receptor subtypes can modulate the specific brain circuits and physiology that are disrupted in schizophrenia and are thought to underlie positive, negative, and cognitive symptoms. Novel therapeutic strategies for targeting these receptors are now advancing in clinical and preclinical development and expand upon the promise of these new treatment strategies to potentially provide more comprehensive relief than currently available antipsychotics.
精神分裂症是一种严重的神经精神疾病，其特征是多种症状，这些症状会对患者的生活产生深远的影响。目前可用的抗精神病药物针对多巴胺受体，虽然它们对改善疾病的阳性症状很有用，但这种方法通常并不能显著改善阴性和认知症状。令人兴奋的是，临床前和临床研究表明，针对特定的毒蕈碱乙酰胆碱受体亚型可能会提供更全面的症状缓解，并有可能改善众多症状领域。机制研究表明，M1、M4 和 M5 受体亚型可以调节在精神分裂症中被打乱的特定大脑回路和生理学，并且被认为是阳性、阴性和认知症状的基础。目前，针对这些受体的新型治疗策略正在临床前和临床开发中推进，并扩大了这些新治疗策略的潜力，有可能提供比目前可用的抗精神病药物更全面的缓解。
