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Cholinergic muscarinic M1 and M4 receptors as therapeutic targets for cognitive, behavioural, and psychological symptoms in psychiatric and neurological disorders

Lookup NU author(s): Dr Daniel ErskineORCiD, Professor John-Paul TaylorORCiD


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Cholinergic dysfunction is involved in a range of neurological and psychiatric disorders, including schizophrenia, dementia and Lewy body disease (LBD), leading to widespread use of cholinergic therapies. However, such drugs have focussed on increasing the availability of acetylcholine (ACh) generally, with relatively little work done on the muscarinic system and specific muscarinic receptor subtypes. In this review, we provide an overview of the major cholinergic pathways and cholinergic muscarinic receptors in the human brain and evidence for their dysfunction in several neurological and psychiatric disorders. We discuss how the selectivity of cholinergic system dysfunction suggests that targeted cholinergic therapeutics to the muscarinic receptor subtypes will be vital in treating several disorders associated with cognitive dysfunction and behavioural and psychological symptoms.

Publication metadata

Author(s): Erskine D, Taylor JP, Bakker G, Brown AJH, Tasker T, Nathan PJ

Publication type: Article

Publication status: Published

Journal: Drug Discovery Today

Year: 2019

Volume: 24

Issue: 12

Pages: 2307-2314

Print publication date: 01/12/2019

Online publication date: 06/09/2019

Acceptance date: 06/09/2019

ISSN (print): 1359-6446

ISSN (electronic): 1878-5832

Publisher: Elsevier


DOI: 10.1016/j.drudis.2019.08.009

PubMed id: 31499186


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