ArticleNeuron2015
Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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
70 citing papers in PubMed, 128 citations in OpenAlex.
- The anti-dyskinetic effect of the clinic-ready mGluRNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Further Optimization of the mGluACS chemical neuroscience · 2025Article
- Conformational diversity in class C GPCR positive allosteric modulation.Nature communications · 2025Article
- mGluR5 as a Potential Orchestrator of Astrocyte Interactions in Neurological Disorders.Neural plasticity · 2025Review
- Discovery of VU6024578/BI02982816: An mGluJournal of medicinal chemistry · 2024Article
- mGluR5 positive allosteric modulation prevents MK-801 induced increases in extracellular glutamate in the rat medial prefrontal cortex.Neuroscience · 2024Article
- Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders.International journal of molecular sciences · 2024Review
- Novel pharmacological targets for GABAergic dysfunction in ADHD.Neuropharmacology · 2024Review
- Gamma oscillation plasticity is mediated via parvalbumin interneurons.Science advances · 2024Article
- The role of neurotrophic factors in novel, rapid psychiatric treatments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Age-related dysregulation of homeostatic control in neuronal microcircuits.Nature neuroscience · 2023Article
- Article
- Role of mGlu5 in Persistent Forms of Hippocampal Synaptic Plasticity and the Encoding of Spatial Experience.Cells · 2022Review
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- Metabotropic Glutamate Receptors As Emerging Targets for the Treatment of Schizophrenia.Molecular pharmacology · 2022Review
- Discovery of "Molecular Switches" within a Series of mGluACS bio & med chem Au · 2021Article
- Activating mGluBiological psychiatry · 2021Article
- Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure.Brain structure & function · 2021Article
- The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment-A Narrative Review.Journal of clinical medicine · 2021Review
- Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.Scientific reports · 2021Article
10 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
30 authors at 2 institutions in 3 countries.
Funding
Abstract
Schizophrenia is associated with disruptions in N-methyl-D-aspartate glutamate receptor subtype (NMDAR)-mediated excitatory synaptic signaling. The metabotropic glutamate receptor subtype 5 (mGlu5) is a closely associated signaling partner with NMDARs and regulates NMDAR function in forebrain regions implicated in the pathology of schizophrenia. Efficacy of mGlu5 positive allosteric modulators (PAMs) in animal models of psychosis and cognition was previously attributed to potentiation of NMDAR function. To directly test this hypothesis, we identified VU0409551 as a novel mGlu5 PAM that exhibits distinct stimulus bias and selectively potentiates mGlu5 coupling to Gαq-mediated signaling but not mGlu5 modulation of NMDAR currents or NMDAR-dependent synaptic plasticity in the rat hippocampus. Interestingly, VU0409551 produced robust antipsychotic-like and cognition-enhancing activity in animal models. These data provide surprising new mechanistic insights into the actions of mGlu5 PAMs and suggest that modulation of NMDAR currents is not critical for in vivo efficacy. VIDEO ABSTRACT.
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What OpenQuestion holds
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.