000279165 001__ 279165 000279165 005__ 20250709100935.0 000279165 0247_ $$2doi$$a10.12688/f1000research.155356.2 000279165 0247_ $$2pmid$$apmid:39844929 000279165 0247_ $$2pmc$$apmc:PMC11751611 000279165 037__ $$aDZNE-2025-00693 000279165 041__ $$aEnglish 000279165 082__ $$a610 000279165 1001_ $$00000-0001-8264-2039$$aSiafis, Spyridon$$b0 000279165 245__ $$aMuscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis [version 2; peer review: 1 approved, 2 approved with reservations] 000279165 260__ $$aLondon$$bF1000 Research Ltd$$c2025 000279165 3367_ $$2DRIVER$$aarticle 000279165 3367_ $$2DataCite$$aOutput Types/Journal article 000279165 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1751965736_3177 000279165 3367_ $$2BibTeX$$aARTICLE 000279165 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000279165 3367_ $$00$$2EndNote$$aJournal Article 000279165 520__ $$aMuscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.We plan a systematic review and meta-analysis of in vivo animal studies comparing muscarinic receptor agonists or positive allosteric modulators with control conditions and existing D2R-blocking antipsychotics in animals subjected to any method that induces behavioural changes of relevance for psychosis. We will identify eligible studies by searching multiple electronic databases. At least two independent reviewers will conduct the study selection and data extraction using prespecified forms and assess the risk of bias with the SYRCLE's tool. Our primary outcomes include locomotor activity and prepulse inhibition measured with standardized mean differences. We will examine other behavioural readouts of relevance for psychosis as secondary outcomes, such as social interaction and cognitive function. We will synthesize the data using multi-level meta-analysis with a predefined random-effects structure, considering the non-independence of the data. In meta-regressions we will explore potential sources of heterogeneity from a predefined list of characteristics of the animal population, model, and intervention. We will assess the confidence in the evidence considering a self-developed instrument thatconsiders the internal and external validity of the evidence.PROSPERO-ID: CRD42024520914. 000279165 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000279165 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000279165 650_7 $$2Other$$aantipsychotic; schizophrenia; psychosis; muscarinic receptor; acetylcholine; meta-analysis 000279165 650_7 $$2NLM Chemicals$$aMuscarinic Agonists 000279165 650_7 $$2NLM Chemicals$$aAntipsychotic Agents 000279165 650_2 $$2MeSH$$aAnimals 000279165 650_2 $$2MeSH$$aSystematic Reviews as Topic 000279165 650_2 $$2MeSH$$aPsychotic Disorders: drug therapy 000279165 650_2 $$2MeSH$$aDisease Models, Animal 000279165 650_2 $$2MeSH$$aMeta-Analysis as Topic 000279165 650_2 $$2MeSH$$aAllosteric Regulation: drug effects 000279165 650_2 $$2MeSH$$aMuscarinic Agonists: therapeutic use 000279165 650_2 $$2MeSH$$aMuscarinic Agonists: pharmacology 000279165 650_2 $$2MeSH$$aAntipsychotic Agents: therapeutic use 000279165 650_2 $$2MeSH$$aAntipsychotic Agents: pharmacology 000279165 7001_ $$aNomura, Nobuyuki$$b1 000279165 7001_ $$00000-0002-3448-9532$$aSchneider-Thoma, Johannes$$b2 000279165 7001_ $$aBighelli, Irene$$b3 000279165 7001_ $$00000-0002-3161-1395$$aBannach-Brown, Alexandra$$b4 000279165 7001_ $$aRamage, Fiona J$$b5 000279165 7001_ $$aTinsdeall, Francesca$$b6 000279165 7001_ $$aMantas, Ioannis$$b7 000279165 7001_ $$aJauhar, Sameer$$b8 000279165 7001_ $$aNatesan, Sridhar$$b9 000279165 7001_ $$aVernon, Anthony C$$b10 000279165 7001_ $$ade Bartolomeis, Andrea$$b11 000279165 7001_ $$00000-0003-4878-5241$$aHölter, Sabine M$$b12 000279165 7001_ $$aDrude, Natascha I$$b13 000279165 7001_ $$aTölch, Ulf$$b14 000279165 7001_ $$aHansen, Wulf-Peter$$b15 000279165 7001_ $$aChiocchia, Virginia$$b16 000279165 7001_ $$aHowes, Oliver D$$b17 000279165 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b18$$udzne 000279165 7001_ $$00000-0001-9187-9839$$aMacleod, Malcolm R$$b19 000279165 7001_ $$00000-0002-3830-8508$$aSalanti, Georgia$$b20 000279165 7001_ $$00000-0002-4934-4352$$aLeucht, Stefan$$b21 000279165 773__ $$0PERI:(DE-600)2699932-8$$a10.12688/f1000research.155356.2$$gVol. 13, p. 1017 -$$p1017$$tF1000Research$$v13$$x2046-1402$$y2025 000279165 8564_ $$uhttps://pub.dzne.de/record/279165/files/DZNE-2025-00693.pdf$$yOpenAccess 000279165 8564_ $$uhttps://pub.dzne.de/record/279165/files/DZNE-2025-00693.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000279165 909CO $$ooai:pub.dzne.de:279165$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000279165 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811122$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b18$$kDZNE 000279165 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0 000279165 9141_ $$y2025 000279165 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-11 000279165 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000279165 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-09-09T10:14:36Z 000279165 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-09-09T10:14:36Z 000279165 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000279165 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Post-publication peer review, Open peer review$$d2024-09-09T10:14:36Z 000279165 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-11 000279165 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-11 000279165 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-11 000279165 9201_ $$0I:(DE-2719)5000007$$kAG Priller$$lTranslational Neuropsychiatry$$x0 000279165 980__ $$ajournal 000279165 980__ $$aVDB 000279165 980__ $$aUNRESTRICTED 000279165 980__ $$aI:(DE-2719)5000007 000279165 9801_ $$aFullTexts