ArticleNeuron2016
Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed.
- Differential and state-dependent effects of the GluN2A-selective positive allosteric modulator GNE-5729 on executive functions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- NMDA Receptor Mediated Mechanisms in the Post-Stroke Brain: From Physiology to Pathology.Biomolecules · 2026Review
- Hypoxia-inducible factor signaling regulates embryonic interneuron development, GRIN2B expression and adult cortical function.Developmental cell · 2026Article
- AMCF-RDP: a self-attention-based multi-source and cascade framework for the identification of drug-protein relationships.Molecular diversity · 2026Article
- GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities inScience advances · 2026Article
- Novel binding mode for negative allosteric NMDA receptor modulators.The Journal of general physiology · 2026Article
- AI-enhanced virtual screening approach to hit identification for GluN1/GluN3A NMDA receptor.Acta pharmacologica Sinica · 2026Article
- Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites.The EMBO journal · 2025Article
- Erasing "bad memories": reversing aberrant synaptic plasticity as therapy for neurological and psychiatric disorders.Molecular psychiatry · 2025Review
- Distinct Regulation of Early Trafficking of the NMDA Receptors by the Ligand-Binding Domains of the GluN1 and GluN2A Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.Molecular psychiatry · 2025Review
- A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.PNAS nexus · 2025Article
- Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Chlorpyrifos Acts as a Positive Modulator and an Agonist ofJournal of xenobiotics · 2025Article
- Evaluation of allosteric N-methyl-d-aspartate receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.Molecular pharmacology · 2025Article
- EAR-20 peptide, a novel NMDA receptor positive allosteric modulator.Frontiers in pharmacology · 2025Article
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- Bi-directional allosteric pathway in NMDA receptor activation and modulation.Nature communications · 2024Article
- Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways.International journal of molecular sciences · 2024Review
- Discovery of GluN2A subtype-selectiveActa pharmaceutica Sinica. B · 2024Review
47 more citing papers are in PubMed but not listed here.
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15 authors.
Funding
Abstract
To enhance physiological function of NMDA receptors (NMDARs), we identified positive allosteric modulators (PAMs) of NMDARs with selectivity for GluN2A subunit-containing receptors. X-ray crystallography revealed a binding site at the GluN1-GluN2A dimer interface of the extracellular ligand-binding domains (LBDs). Despite the similarity between the LBDs of NMDARs and AMPA receptors (AMPARs), GluN2A PAMs with good selectivity against AMPARs were identified. Potentiation was observed with recombinant triheteromeric GluN1/GluN2A/GluN2B NMDARs and with synaptically activated NMDARs in brain slices from wild-type (WT), but not GluN2A knockout (KO), mice. Individual GluN2A PAMs exhibited variable degrees of glutamate (Glu) dependence, impact on NMDAR Glu EC50, and slowing of channel deactivation. These distinct PAMs also exhibited differential impacts during synaptic plasticity induction. The identification of a new NMDAR modulatory site and characterization of GluN2A-selective PAMs provide powerful molecular tools to dissect NMDAR function and demonstrate the feasibility of a therapeutically desirable type of NMDAR enhancement.
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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.