ArticleNeuron2016
Antipsychotic-like Effects of M4 Positive Allosteric Modulators Are Mediated by CB2 Receptor-Dependent Inhibition of Dopamine Release.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
103 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Is muscarinic receptor agonist effective and tolerant for schizophrenia?BMC psychiatry · 2025Pooled it
- Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review.CNS drugs · 2022Pooled it
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2.Journal of medicinal chemistry · 2026Article
- Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?Current neuropharmacology · 2026Review
- Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Beyond dopamine: KarXT and emerging mechanism-based therapies in schizophrenia.Frontiers in psychiatry · 2026Review
- Neuronal versus Glial CB2 Receptors: Insights from a Novel CB2-KO-eGFP Reporter Mouse Line.Research square · 2025Article
- Discovery of Pre-Clinical CandidateACS chemical neuroscience · 2025Article
- Downstream Signaling of Muscarinic MPharmacology research & perspectives · 2025Article
- Does Dysregulation Of The Indirect Pathway Contribute To The Pathophysiology Of Catatonia Through Neurotransmitter Imbalance?Clinical neuropsychiatry · 2025Article
- Characterization of Novel and Known Activators of Cannabinoid Receptor Subtype 2 Reveals Mixed Pharmacology That Differentiates Mycophenolate Mofetil and GW-842,166X from MDA7.International journal of molecular sciences · 2025Article
- A New Era of Muscarinic Acetylcholine Receptor Modulators in Neurological Diseases, Cancer and Drug Abuse.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Further Optimization of the mGluACS chemical neuroscience · 2025Article
- Cholinergic System Structure and Function Changes in Individuals with Down Syndrome During the Development of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Behavioral signature of trihexyphenidyl in theDystonia (Lausanne, Switzerland) · 2025Article
- Discovery of VU6024578/BI02982816: An mGluJournal of medicinal chemistry · 2024Article
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- Reduced striatal M4-cholinergic signaling following dopamine loss contributes to parkinsonian and l-DOPA-induced dyskinetic behaviors.Science advances · 2024Article
- G protein-coupled receptor modulation of striatal dopamine transmission: Implications for psychoactive drug effects.British journal of pharmacology · 2024Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Muscarinic receptors represent a promising therapeutic target for schizophrenia, but the mechanisms underlying the antipsychotic efficacy of muscarinic modulators are not well understood. Here, we report that activation of M4 receptors on striatal spiny projection neurons results in a novel form of dopaminergic regulation resulting in a sustained depression of striatal dopamine release that is observed more than 30 min after removal of the muscarinic receptor agonist. Furthermore, both the M4-mediated sustained inhibition of dopamine release and the antipsychotic-like efficacy of M4 activators were found to require intact signaling through CB2 cannabinoid receptors. These findings highlight a novel mechanism by which striatal cholinergic and cannabinoid signaling leads to sustained reductions in dopaminergic transmission and concurrent behavioral effects predictive of antipsychotic efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.