ArticleThe Journal of physiology1996
A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones.
Article in The Journal of physiology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 239 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- Kinetic Benefit(s) of Allosteric Receptor Blockade by Positive Allosteric Modulator Antagonists.ACS pharmacology & translational science · 2026Review
- Inhibition of GluN2B-containing N-methyl-D-aspartate receptors by radiprodil.Brain : a journal of neurology · 2026Article
- GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities inScience advances · 2026Article
- Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites.The EMBO journal · 2025Article
- Evaluation of allosteric N-methyl-d-aspartate receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.Molecular pharmacology · 2025Article
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions.Frontiers in pharmacology · 2022Review
- A GlutamateThe Journal of pharmacology and experimental therapeutics · 2021Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Ifenprodil Reduced Expression of Activated Microglia, BDNF and DREAM Proteins in the Spinal Cord Following Formalin Injection During the Early Stage of Painful Diabetic Neuropathy in Rats.Journal of molecular neuroscience : MN · 2021Article
- Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice.PLoS biology · 2020Article
- Synthesis and Preliminary Evaluations of a Triazole-Cored Antagonist as a PET Imaging Probe ([ACS chemical neuroscience · 2019Article
- Analytical Pharmacology: How Numbers Can Guide Drug Discovery.ACS pharmacology & translational science · 2019Review
- Synthesis and receptor binding of thiophene bioisosteres of potent GluN2B ligands with a benzo[7]annulene-scaffold.MedChemComm · 2019Article
- Extrasynaptic NMDA Receptors on Rod Pathway Amacrine Cells: Molecular Composition, Activation, and Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- A structurally derived model of subunit-dependent NMDA receptor function.The Journal of physiology · 2018Article
- Article
- Long-Term Depression Is Independent of GluN2 Subunit Composition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
23 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Ifenprodil is a selective, atypical non-competitive antagonist of NMDA receptors that contain the NR2B subunit with an undefined mechanism of action. Ifenprodil is neuroprotective in in vivo models of cerebral ischaemia but lacks many of the undesirable side-effects associated with NMDA antagonist. 2. Using whole-cell voltage-clamp recordings, we have studied the mechanism of inhibition of NMDA-evoked currents by ifenprodil in rat cultured cortical neurones in the presence of saturating concentrations of glycine. 3. Ifenprodil antagonized NMDA receptors in an activity-dependent manner, whilst also increasing the receptor affinity for glutamate recognition-site agonists. Ifenprodil inhibition curves against 10 and 100 microM NMDA-evoked currents yielded IC50 values of 0.88 and 0.17 microM, respectively. Thus, the apparent affinity of ifenprodil for the NMDA receptor is increased in an NMDA concentration-dependent manner. 4. Currents evoked by 0.3 and 1 microM NMDA were potentiated to approximately 200% of control levels in the presence of 3 microM ifenprodil. Thus, with increasing concentration of NMDA the effect of ifenprodil on NMDA-evoked currents changed from one of potentiation to one of increasing inhibition. 5. These results are predicted by a reaction scheme in which ifenprodil exhibits a 39- and 50-fold higher affinity for the agonist-bound activated and desensitized states of the NMDA receptor, respectively, relative to the resting, agonist-unbound state. Furthermore, ifenprodil binding to the NMDA receptor results in a 6-fold higher affinity for glutamate site agonists. 6. This represents a novel mechanism of NMDA receptor antagonism that, together with the subunit selectivity, probably contributes to the attractive neuropharmacological profile of this and related compounds.
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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.