{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:40:11Z","timestamp":1789810811079,"version":"4.0.1"},"reference-count":28,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":2438,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["slas-discovery.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["SLAS Discovery"],"published-print":{"date-parts":[[2015,8]]},"DOI":"10.1177\/1087057115581770","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T23:42:52Z","timestamp":1429141372000},"page":"858-868","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4)"],"prefix":"10.1016","volume":"20","author":[{"given":"Emery","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Niswender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Utley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Sheffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith J.","family":"Noetzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atin","family":"Lamsal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Jeffrey","family":"Conn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Lindsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Madoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Scampavia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Spicer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hodder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1177\/1087057115581770_bib1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nrd913","article-title":"G-Protein-Coupled Receptor Oligomerization and Its Potential for Drug Discovery","volume":"1","author":"George","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1177\/1087057115581770_bib2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.pharmtox.41.1.593","article-title":"Genetic Variations and Polymorphisms of G Protein-Coupled Receptors: Functional and Therapeutic Implications","volume":"41","author":"Rana","year":"2001","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1177\/1087057115581770_bib3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0165-6147(00)01636-9","article-title":"Orphan G-Protein-Coupled Receptors and Natural Ligand Discovery","volume":"22","author":"Howard","year":"2001","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1177\/1087057115581770_bib4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd2760","article-title":"Allosteric Modulators of GPCRs: A Novel Approach for the Treatment of CNS Disorders","volume":"8","author":"Jeffrey Conn","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1177\/1087057115581770_bib5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.tips.2008.10.006","article-title":"Activation of Metabotropic Glutamate Receptors as a Novel Approach for the Treatment of Schizophrenia","volume":"30","author":"Conn","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1177\/1087057115581770_bib6","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.2174\/138161206778522056","article-title":"Muscarinic Acetylcholine Receptors","volume":"12","author":"Ishii","year":"2006","journal-title":"Curr. Pharmaceut. Des."},{"key":"10.1177\/1087057115581770_bib7","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.pharmthera.2007.09.009","article-title":"Muscarinic Acetylcholine Receptors as CNS Drug Targets","volume":"117","author":"Langmead","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"10.1177\/1087057115581770_bib8","first-page":"CD003735","article-title":"Anticholinergics for Symptomatic Management of Parkinson\u2019s Disease","volume":"3","author":"Katzenschlager","year":"2002","journal-title":"Cochrane Database Sys. Rev."},{"key":"10.1177\/1087057115581770_bib9","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/cmdc.201402051","article-title":"Discovery, Synthesis and Characterization of a Highly Muscarinic Acetylcholine Receptor (mAChR)-Selective M5-Orthosteric Antagonist, VU0488130 (ML381): A Novel Molecular Probe","volume":"9","author":"Gentry","year":"2014","journal-title":"ChemMedChem."},{"key":"10.1177\/1087057115581770_bib10","first-page":"207","article-title":"Quantifying Bioactivity on a Large Scale: Quality Assurance and Analysis of Multiparametric Ultra-HTS Data","volume":"10","author":"Heyse","year":"2005","journal-title":"J. La. Automat."},{"key":"10.1177\/1087057115581770_bib11","series-title":"Probe Reports from the NIH Molecular Libraries Program","article-title":"Discovery of a Highly Selective In Vitro and In Vivo M4 Positive Allosteric Modulator (PAM)","author":"Lewis","year":"2010"},{"key":"10.1177\/1087057115581770_bib12","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/363274a0","article-title":"Substitution of Three Amino Acids Switches Receptor Specificity of Gq Alpha to That of Gi Alpha","volume":"363","author":"Conklin","year":"1993","journal-title":"Nature"},{"key":"10.1177\/1087057115581770_bib13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J. Biomol. Screen."},{"key":"10.1177\/1087057115581770_bib14","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1177\/1087057114525852","article-title":"Identification of Potent and Selective Inhibitors of the Plasmodium falciparum M18 Aspartyl Aminopeptidase (PfM18AAP) of Human Malaria via High-Throughput Screening","volume":"19","author":"Spicer","year":"2014","journal-title":"J. Biomol. Screen."},{"key":"10.1177\/1087057115581770_bib15","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1177\/1087057114542975","article-title":"Identification of Selective Agonists and Positive Allosteric Modulators for Micro- and Delta-Opioid Receptors from a Single High-Throughput Screen","volume":"19","author":"Burford","year":"2014","journal-title":"J. Biomol. Screen."},{"key":"10.1177\/1087057115581770_bib16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/adt.2009.0245","article-title":"A Multiplex Calcium Assay for Identification of GPCR Agonists and Antagonists","volume":"8","author":"Liu","year":"2010","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1177\/1087057115581770_bib17","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/cmdc.200600134","article-title":"The 7 TM G-Protein-Coupled Receptor Target Family","volume":"1","author":"Jacoby","year":"2006","journal-title":"ChemMedChem."},{"key":"10.1177\/1087057115581770_bib18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1124\/mol.110.067207","article-title":"Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity","volume":"78","author":"Rodriguez","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"10.1177\/1087057115581770_bib19","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1089\/adt.2011.443","article-title":"Development of a High-Throughput Calcium Flux Assay for Identification of All Ligand Types Including Positive, Negative, and Silent Allosteric Modulators for G Protein-Coupled Receptors","volume":"10","author":"Noblin","year":"2012","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1177\/1087057115581770_bib20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1124\/mol.109.058677","article-title":"Selective and Brain Penetrant Neuropeptide y y2 Receptor Antagonists Discovered by Whole-Cell High-Throughput Screening","volume":"77","author":"Brothers","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"10.1177\/1087057115581770_bib21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0003-2697(02)00608-5","article-title":"Identification of Metabotropic Glutamate Receptor Antagonists Using an Automated High-Throughput Screening System","volume":"313","author":"Hodder","year":"2003","journal-title":"Anal. Biochem."},{"key":"10.1177\/1087057115581770_bib22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1124\/mol.111.075184","article-title":"Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function","volume":"81","author":"Noetzel","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"10.1177\/1087057115581770_bib23","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tips.2008.12.002","article-title":"Subtype-Selective Allosteric Modulators of Muscarinic Receptors for the Treatment of CNS Disorders","volume":"30","author":"Conn","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1177\/1087057115581770_bib24","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bmcl.2014.11.011","article-title":"Discovery and SAR of Muscarinic Receptor Subtype 1 (M) Allosteric Activators from a Molecular Libraries High Throughput Screen. Part 1: 2,5-Dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as Positive Allosteric Modulators","volume":"25","author":"Han","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1177\/1087057115581770_bib25","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1124\/mol.107.041053","article-title":"A Novel Assay of Gi\/o-Linked G Protein-Coupled Receptor Coupling to Potassium Channels Provides New Insights into the Pharmacology of the Group III Metabotropic Glutamate Receptors","volume":"73","author":"Niswender","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"10.1177\/1087057115581770_bib26","series-title":"Discovery, Optimization, and Characterization of Novel Subtype-Selective M5 Muscarinic Acetylcholine Receptor Ligands; Ph.D. Thesis","author":"Gentry","year":"2014"},{"key":"10.1177\/1087057115581770_bib27","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1016\/j.bmcl.2010.12.015","article-title":"Discovery and Optimization of a Novel, Selective and Brain Penetrant M1 Positive Allosteric Modulator (PAM): The Development of ML169, an MLPCN Probe","volume":"21","author":"Reid","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1177\/1087057115581770_bib28","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/cmdc.201402051","article-title":"Discovery, Synthesis and Characterization of a Highly Muscarinic Acetylcholine Receptor (mAChR)-Selective M5-Orthosteric Antagonist, VU0488130 (ML381): A Novel Molecular Probe","volume":"9","author":"Gentry","year":"2014","journal-title":"ChemMedChem."}],"container-title":["SLAS Discovery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1087057115581770","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1087057115581770","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2472555222072549?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2472555222072549?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1087057115581770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:41:22Z","timestamp":1762861282000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2472555222072549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["S2472555222072549"],"URL":"https:\/\/doi.org\/10.1177\/1087057115581770","relation":{},"ISSN":["2472-5552"],"issn-type":[{"value":"2472-5552","type":"print"}],"subject":[],"published":{"date-parts":[[2015,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4)","name":"articletitle","label":"Article Title"},{"value":"SLAS Discovery","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1177\/1087057115581770","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 Society for Laboratory Automation and Screening. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}