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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$$c2025
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000279165 520__ $$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.
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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
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