ArticleNeuron2015
Context-dependent GluN2B-selective inhibitors of NMDA receptor function are neuroprotective with minimal side effects.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 69 citations in OpenAlex.
- Inhibition of GluN2B-containing N-methyl-D-aspartate receptors by radiprodil.Brain : a journal of neurology · 2026Article
- Ischemic stroke triggers brain-wide synaptic remodeling within four hours.PLoS biology · 2026Article
- Accommodating Statistical and Physics-Based Computational Protocols for Molecular Glue Model and Evaluation.Journal of chemical information and modeling · 2025Article
- How to Pick a Neuroprotective Drug in Stroke Without Losing Your Mind?Life (Basel, Switzerland) · 2025Review
- Reversible Control of Native GluN2B-Containing NMDA Receptors with Visible Light.ACS chemical neuroscience · 2024Article
- Chronic exposure to tris (2-chloroethyl) phosphate (TCEP) induces brain structural and functional changes in zebrafish (Danio rerio): A comparative study on the environmental and LC50 concentrations of TCEP.Environmental science and pollution research international · 2024Article
- Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs.Cell reports · 2024Article
- Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives.Molecular neurobiology · 2023Article
- Targeting Striatal Glutamate and Phosphodiesterases to Control L-DOPA-Induced Dyskinesia.Cells · 2023Review
- GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor.Clinical pharmacology in drug development · 2023Article
- Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model.ACS chemical neuroscience · 2023Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- A GlutamateThe Journal of pharmacology and experimental therapeutics · 2021Article
- Bidentatide, a Novel Plant Peptide Derived fromInternational journal of molecular sciences · 2021Article
- The Negative Allosteric Modulator EU1794-4 Reduces Single-Channel Conductance and CaMolecular pharmacology · 2021Article
- Icaritin Alleviates Glutamate-Induced Neuronal Damage by Inactivating GluN2B-Containing NMDARs Through the ERK/DAPK1 Pathway.Frontiers in neuroscience · 2021Article
- NMDA receptor channel gating control by the pre-M1 helix.The Journal of general physiology · 2020Article
- Excitotoxicity: Still Hammering the Ischemic Brain in 2020.Frontiers in neuroscience · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Stroke remains a significant problem despite decades of work on neuroprotective strategies. NMDA receptor (NMDAR) antagonists are neuroprotective in preclinical models, but have been clinically unsuccessful, in part due to side effects. Here we describe a prototypical GluN2B-selective antagonist with an IC50 value that is 10-fold more potent at acidic pH 6.9 associated with ischemic tissue compared to pH 7.6, a value close to the pH in healthy brain tissue. This should maximize neuroprotection in ischemic tissue while minimizing on-target side effects associated with NMDAR blockade in noninjured brain regions. We have determined the mechanism underlying pH-dependent inhibition and demonstrate the utility of this approach in vivo. We also identify dicarboxylate dimers as a novel proton sensor in proteins. These results provide insight into the molecular basis of pH-dependent neuroprotective NMDAR block, which could be beneficial in a wide range of neurological insults associated with tissue acidification.
Indexed as
Identifiers
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.