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Title: A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia.
Austin Authors: Dean, Brian;Bakker, Geor;Ueda, Hiroki R;Tobin, Andrew B;Brown, Alastair;Kanaan, Richard A A 
Affiliation: Synaptic Biology and Cognition Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
Sosei Heptares, Cambridge, United Kingdom.
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Advanced Research Centre (ARC), School of Molecular Bioscience, University of Glasgow, Glasgow, United Kingdom.
Sosei Heptares, Cambridge, United Kingdom.
Psychiatry (University of Melbourne)
Issue Date: 2023
Date: 2023
Publication information: Frontiers in Cellular Neuroscience 2023; 17: 1124333
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.
DOI: 10.3389/fncel.2023.1124333
Journal: Frontiers in Cellular Neuroscience
Start page: 1124333
PubMed URL: 36909280
Type: Journal Article
Subjects: KarXT
muscarinic M1 receptor
muscarinic M4 receptor
postmortem CNS
Appears in Collections:Journal articles

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