ArticleNeuron2016
Structural Bases of Noncompetitive Inhibition of AMPA-Subtype Ionotropic Glutamate Receptors by Antiepileptic Drugs.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- AMPA Receptor Modulation Through Medium-Chain Triglycerides and Decanoic Acid Supports Nutritional Intervention in Pediatric Epilepsy.Nutrients · 2025Pooled it
- Tuning of AMPA receptor activation by inhibitory auxiliary subunits and epilepsy-associated disease mutations.Nature communications · 2026Article
- Phenytoin Derivatives as Antagonists of AMPA Receptors and Voltage-Gated Sodium Channels: A Structure-Function Study.International journal of molecular sciences · 2026Article
- N-Methyl-D-aspartate receptors: structure, signaling and roles in atherosclerosis.Journal of translational medicine · 2026Review
- Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core.Nature communications · 2026Article
- Robust PHP in Adult Hippocampus: Essential Assay Optimizations.bioRxiv : the preprint server for biology · 2026Article
- Auxiliary TARP Subunits Define AMPA Receptor Pharmacology and Function.Journal of xenobiotics · 2026Article
- Design, Docking, Synthesis, and Biological Evaluation of Pyrazolone Derivatives as Potential Dual-Action Antimicrobial and Antiepileptic Agents.Pharmaceuticals (Basel, Switzerland) · 2026Article
- JNJ-55511118 Stabilizes a Desensitized-like Conformation of γ8-Containing AMPA Receptors through Long-Range Allosteric Modulation.bioRxiv : the preprint server for biology · 2025Article
- The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.Nature communications · 2025Article
- Clinical and Neurodevelopmental Characteristics of Paralogous Gain-of-Function Variants at GRIA2 p.Gly792 and GRIA3 p.Gly803.Clinical genetics · 2025Article
- Activation of kainate receptor GluK2-Neto2 complex.Nature structural & molecular biology · 2025Article
- Article
- GluK2 kainate receptor subunit-selective, potentiating RNA aptamer.Scientific reports · 2025Article
- Article
- Endothelium glutamate receptors in brain pathology.Frontiers in pharmacology · 2025Review
- Structure and gating of kainate receptors.Frontiers in pharmacology · 2025Review
- Trapping of spermine, Kukoamine A, and polyamine toxin blockers in GluK2 kainate receptor channels.Nature communications · 2024Article
- Allosteric competition and inhibition in AMPA receptors.Nature structural & molecular biology · 2024Article
- Temperature Sensitive Glutamate Gating of AMPA-subtype iGluRs.bioRxiv : the preprint server for biology · 2024Article
20 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Excitatory neurotransmission plays a key role in epileptogenesis. Correspondingly, AMPA-subtype ionotropic glutamate receptors, which mediate the majority of excitatory neurotransmission and contribute to seizure generation and spread, have emerged as promising targets for epilepsy therapy. The most potent and well-tolerated AMPA receptor inhibitors act via a noncompetitive mechanism, but many of them produce adverse side effects. The design of better drugs is hampered by the lack of a structural understanding of noncompetitive inhibition. Here, we report crystal structures of the rat AMPA-subtype GluA2 receptor in complex with three noncompetitive inhibitors. The inhibitors bind to a novel binding site, completely conserved between rat and human, at the interface between the ion channel and linkers connecting it to the ligand-binding domains. We propose that the inhibitors stabilize the AMPA receptor closed state by acting as wedges between the transmembrane segments, thereby preventing gating rearrangements that are necessary for ion channel opening.
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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.