{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:06:23Z","timestamp":1792796783138,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["19-05318S"],"award-info":[{"award-number":["19-05318S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004240","name":"Akademie v\u011bd \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["RVO:67985823"],"award-info":[{"award-number":["RVO:67985823"]}],"id":[{"id":"10.13039\/501100004240","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated G-protein-coupled receptors. They are a potential therapeutic target for the treatment of psychiatric, neurologic, and internal diseases like schizophrenia, Alzheimer\u2019s disease, Huntington disease, type 2 diabetes, or chronic pulmonary obstruction. Here, we reviewed the progress made during the last decade in our understanding of their mechanisms of binding, allosteric modulation, and in vivo actions in order to understand the translational impact of studying this important class of pharmacological agents. We overviewed newly developed allosteric modulators of muscarinic receptors as well as new spin-off ideas like bitopic ligands combining allosteric and orthosteric moieties and photo-switchable ligands based on bitopic agents.<\/jats:p>","DOI":"10.3390\/biom10020325","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T10:49:16Z","timestamp":1582282156000},"page":"325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Current Advances in Allosteric Modulation of Muscarinic Receptors"],"prefix":"10.3390","volume":"10","author":[{"given":"Jan","family":"Jakubik","sequence":"first","affiliation":[{"name":"Department of Neurochemistry, Institute of Physiology CAS, 142 20 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esam E.","family":"El-Fakahany","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1126\/science.3037705","article-title":"Identification of a family of muscarinic acetylcholine receptor genes","volume":"237","author":"Bonner","year":"1987","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10753","article-title":"Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist","volume":"482","author":"Haga","year":"2012","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nature10867","article-title":"Structure and dynamics of the M3 muscarinic acetylcholine receptor","volume":"482","author":"Kruse","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature12735","article-title":"Activation and allosteric modulation of a muscarinic acetylcholine receptor","volume":"504","author":"Kruse","year":"2013","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature17188","article-title":"Crystal structures of the M1 and M4 muscarinic acetylcholine receptors","volume":"531","author":"Thal","year":"2016","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26001","DOI":"10.1073\/pnas.1914446116","article-title":"Crystal structure of the M5 muscarinic acetylcholine receptor","volume":"116","author":"Vuckovic","year":"2019","journal-title":"Proc. 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