ABSTRACT Over the past 40 years, the muscarinic acetylcholine receptor family, particularly the M1-receptor and M4-receptor subtypes, have emerged as validated targets for the symptomatic

treatment of neurological diseases such as schizophrenia and Alzheimer disease. However, despite considerable effort and investment, no drugs have yet gained clinical approval. This is

largely attributable to cholinergic adverse effects that have halted the majority of programmes and resulted in a waning of interest in these G-protein-coupled receptor targets. Recently,

this trend has been reversed. Driven by advances in structure-based drug design and an appreciation of the optimal pharmacological properties necessary to deliver clinical efficacy while

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ACETYLCHOLINE RECEPTOR M4R BY DIVERSE LIGANDS Article Open access 23 May 2022 XANOMELINE DISPLAYS CONCOMITANT ORTHOSTERIC AND ALLOSTERIC BINDING MODES AT THE M4 MACHR Article Open access 06

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PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS The author thanks the Wellcome Trust, who provided a Collaborative Award (201529/Z/16/Z) to A.B.T., and the generous 

donations of the Rice family, and Alan and Ann Boyd. Thanks also to C. Jones (Vanderbilt University) for proofreading and advice. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Centre for

Translational Pharmacology, School of Molecular Biosciences, The Advanced Research Centre, University of Glasgow, Glasgow, UK Andrew B. Tobin Authors * Andrew B. Tobin View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Andrew B. Tobin. ETHICS DECLARATIONS COMPETING INTERESTS A.T. is fully

employed by the University of Glasgow but is also co-founder and CEO of the spin-out company Keltic Pharma Therapeutics Ltd, which has an interest in targeting muscarinic receptors in

neurological disease. PEER REVIEW PEER REVIEW INFORMATION _Nature Reviews Drug Discovery_ thanks Jan Jakubik, Daniel Foster and Christian Felder for their contribution to the peer review of

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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tobin, A.B. A golden age of muscarinic acetylcholine receptor modulation in neurological diseases. _Nat Rev Drug

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