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Low Agonism and Balanced Pathway Modulation Distinguish an M1 Muscarinic Receptor Positive Allosteric Modulator Lacking Cholinergic Adverse Effects.

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Title: Low Agonism and Balanced Pathway Modulation Distinguish an M1 Muscarinic Receptor Positive Allosteric Modulator Lacking Cholinergic Adverse Effects.
Authors: Nguyen HTM; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Khajehali E; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Pham V; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Scott JW; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Dite TA; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia., Dagley LF; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia., Murphy JM; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia., Thompson G; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Tobin AB; Centre for Translational Pharmacology, University of Glasgow, Glasgow G12 8QQ, U.K., Thal DM; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Christopoulos A; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia., van der Westhuizen ET; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia., Valant C; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.
Source: ACS chemical neuroscience [ACS Chem Neurosci] 2026 Jul 15; Vol. 17 (14), pp. 2641-2659. Date of Electronic Publication: 2026 Jun 30.
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE
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  Data: <searchLink fieldCode="AU" term="%22Nguyen+HTM%22">Nguyen HTM</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Khajehali+E%22">Khajehali E</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Pham+V%22">Pham V</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Scott+JW%22">Scott JW</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Dite+TA%22">Dite TA</searchLink>; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Dagley+LF%22">Dagley LF</searchLink>; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Murphy+JM%22">Murphy JM</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Thompson+G%22">Thompson G</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Tobin+AB%22">Tobin AB</searchLink>; Centre for Translational Pharmacology, University of Glasgow, Glasgow G12 8QQ, U.K.<br /><searchLink fieldCode="AU" term="%22Thal+DM%22">Thal DM</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Christopoulos+A%22">Christopoulos A</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22van+der+Westhuizen+ET%22">van der Westhuizen ET</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.<br /><searchLink fieldCode="AU" term="%22Valant+C%22">Valant C</searchLink>; Drug Discovery Biology, Monash University, Parkville, Melbourne, Victoria 3052, Australia.; Neuromedicines Discovery Centre, Monash University, Parkville, Melbourne, Victoria 3052, Australia.
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              Text: 2026 Jul 15
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