ReviewProgress in neuro-psychopharmacology & biological psychiatry2015
Perspectives on the mGluR2/3 agonists as a therapeutic target for schizophrenia: Still promising or a dead end?
Review in Progress in neuro-psychopharmacology & biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.Molecular psychiatry · 2022Trial
- Discovery of VU6066098: A Selective and CNS-Penetrant mGluACS chemical neuroscience · 2026Article
- Antipsychotic Drug Action, Novel Treatment Targets, and the Failure of Current Clinical Trial Designs in Evaluating New Target Molecules.Biological psychiatry · 2026Review
- Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics' Regulation of Synaptic Plasticity and Metaplasticity.Biomolecules · 2026Review
- Decoding GPCR signaling in living cells to advance early therapeutic discovery for neurological disorders.Frontiers in molecular neuroscience · 2026Review
- Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.Translational psychiatry · 2025Review
- Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses.Glia · 2024Article
- Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators.International journal of molecular sciences · 2024Review
- Radiosynthesis and Evaluation of 11C-Labeled Isoindolone-Based Positive Allosteric Modulators for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor 2.ACS pharmacology & translational science · 2024Article
- Impairments in the early consolidation of spatial memories via group II mGluR agonism in the mammillary bodies.Scientific reports · 2024Article
- The mGluRNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Effects of the mGlu2/3 receptor agonist LY379268 on two models of disturbed auditory evoked brain oscillations in mice.Translational psychiatry · 2023Article
- Neurotoxic/Neuroprotective Effects of Clozapine and the Positive Allosteric Modulator of mGluR2 JNJ-46356479 in Human Neuroblastoma Cell Cultures.International journal of molecular sciences · 2023Article
- The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia.International journal of molecular sciences · 2023Article
- Review
- LY395756 promotes NR2B expression via activation of AKT/CREB signaling in the juvenile methylazoxymethanol mice model of schizophrenia.Brain and behavior · 2022Article
- Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia.Translational psychiatry · 2021Review
- The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment-A Narrative Review.Journal of clinical medicine · 2021Review
- Regulation of Glutamatergic Activity via Bidirectional Activation of Two Select Receptors as a Novel Approach in Antipsychotic Drug Discovery.International journal of molecular sciences · 2020Review
- NMDA receptor hypofunction for schizophrenia revisited: Perspectives from epigenetic mechanisms.Schizophrenia research · 2020Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Group II metabotropic glutamate receptor (mGluR2/3) agonists once showed promise as non-dopaminergic antipsychotic drugs because of their efficacy in alleviating symptoms of schizophrenia (SZ) in both animal models and human patients. However, the recent failure of Phase III clinical trials dealt a huge blow to the scientific community and the aftershock of the setback in mGluR2/3 research can be felt everywhere from grant support and laboratory studies to paper publication. An immediate question raised is whether mGluR2/3 is still a promising therapeutic target for schizophrenia. Answering this question is not easy, but apparently a new strategy is needed. This article provides a focused review of literature on the study of mGluR2/3 agonists, especially on mGluR2/3 agonists' mechanism of action and efficacy in both normal conditions and animal models of SZ, as well as clinical studies in human patients with the disease. We argue that the cellular and molecular actions of mGluR2/3 agonists, the distinct roles between mGluR2 and mGluR3, as well as their effects on different stages of the disease and different subpopulations of patients, remain incompletely studied. Until the mechanisms associated with mGluR2/3 are clearly elucidated and all treatment options are tested, it would be a great mistake to terminate the study of mGluR2/3 as a therapeutic target for schizophrenia. This review will thus shed light on the comprehensive features of the translational potential mGluR2/3 agonists as well as the need for further research into the more selective activation of mGluR2.
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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.