Muscarinic 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]
Background Muscarinic 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 i...
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2025-01-01
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| author | Spyridon Siafis Johannes Schneider-Thoma Alexandra Bannach-Brown Oliver D. Howes Virginia Chiocchia Ulf Tölch Natascha I. Drude Sabine M. Hölter Andrea de Bartolomeis Anthony C. Vernon Georgia Salanti Sridhar Natesan Stefan Leucht Irene Bighelli Sameer Jauhar Ioannis Mantas Josef Priller Francesca Tinsdeall Wulf-Peter Hansen Fiona J. Ramage Nobuyuki Nomura Malcolm R. Macleod |
| author_facet | Spyridon Siafis Johannes Schneider-Thoma Alexandra Bannach-Brown Oliver D. Howes Virginia Chiocchia Ulf Tölch Natascha I. Drude Sabine M. Hölter Andrea de Bartolomeis Anthony C. Vernon Georgia Salanti Sridhar Natesan Stefan Leucht Irene Bighelli Sameer Jauhar Ioannis Mantas Josef Priller Francesca Tinsdeall Wulf-Peter Hansen Fiona J. Ramage Nobuyuki Nomura Malcolm R. Macleod |
| author_sort | Spyridon Siafis |
| collection | DOAJ |
| description | Background Muscarinic 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. Methods 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. Protocol registration PROSPERO-ID: CRD42024520914 |
| format | Article |
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| institution | Kabale University |
| issn | 2046-1402 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | F1000 Research Ltd |
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| series | F1000Research |
| spelling | doaj-art-701c1c0279bb45f2861c199cba7cbd422025-01-22T01:00:02ZengF1000 Research LtdF1000Research2046-14022025-01-0113176234Muscarinic 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]Spyridon Siafis0https://orcid.org/0000-0001-8264-2039Johannes Schneider-Thoma1https://orcid.org/0000-0002-3448-9532Alexandra Bannach-Brown2https://orcid.org/0000-0002-3161-1395Oliver D. Howes3Virginia Chiocchia4Ulf Tölch5Natascha I. Drude6Sabine M. Hölter7https://orcid.org/0000-0003-4878-5241Andrea de Bartolomeis8Anthony C. Vernon9Georgia Salanti10https://orcid.org/0000-0002-3830-8508Sridhar Natesan11Stefan Leucht12https://orcid.org/0000-0002-4934-4352Irene Bighelli13Sameer Jauhar14Ioannis Mantas15Josef Priller16Francesca Tinsdeall17Wulf-Peter Hansen18Fiona J. Ramage19Nobuyuki Nomura20Malcolm R. Macleod21https://orcid.org/0000-0001-9187-9839German Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyQUEST Center for Responsible Research, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, GermanyPsychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UKInstitute of Social and Preventive Medicine (ISPM), University of Bern, Bern, SwitzerlandQUEST Center for Responsible Research, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, GermanyQUEST Center for Responsible Research, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanySection of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Dentistry, University Medical School of Naples "Federico II", Naples, ItalyMRC Centre for Neurodevelopmental Disorders, King's College London, London, UKInstitute of Social and Preventive Medicine (ISPM), University of Bern, Bern, SwitzerlandPsychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UKGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyDepartment of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UKDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyCentre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UKBASTA-Bündnis für psychisch erkrankte Menschen, Munich, GermanyCentre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UKGerman Center for Mental Health (DZPG), partner site München/Augsburg, Munich, GermanyCentre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UKBackground Muscarinic 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. Methods 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. Protocol registration PROSPERO-ID: CRD42024520914https://f1000research.com/articles/13-1017/v2antipsychotic; schizophrenia; psychosis; muscarinic receptor; acetylcholine; meta-analysiseng |
| spellingShingle | Spyridon Siafis Johannes Schneider-Thoma Alexandra Bannach-Brown Oliver D. Howes Virginia Chiocchia Ulf Tölch Natascha I. Drude Sabine M. Hölter Andrea de Bartolomeis Anthony C. Vernon Georgia Salanti Sridhar Natesan Stefan Leucht Irene Bighelli Sameer Jauhar Ioannis Mantas Josef Priller Francesca Tinsdeall Wulf-Peter Hansen Fiona J. Ramage Nobuyuki Nomura Malcolm R. Macleod Muscarinic 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] F1000Research antipsychotic; schizophrenia; psychosis; muscarinic receptor; acetylcholine; meta-analysis eng |
| title | Muscarinic 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] |
| title_full | Muscarinic 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] |
| title_fullStr | Muscarinic 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] |
| title_full_unstemmed | Muscarinic 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] |
| title_short | Muscarinic 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] |
| title_sort | muscarinic 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 |
| topic | antipsychotic; schizophrenia; psychosis; muscarinic receptor; acetylcholine; meta-analysis eng |
| url | https://f1000research.com/articles/13-1017/v2 |
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