ArticlePloS one2016
MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- Novel binding mode for negative allosteric NMDA receptor modulators.The Journal of general physiology · 2026Article
- Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites.The EMBO journal · 2025Article
- Advances in the Structural Basis of GluN2A-Selective Negative Allosteric Modulators.ACS medicinal chemistry letters · 2025Article
- Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.Cell reports · 2025Article
- Evaluation of allosteric N-methyl-d-aspartate receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.Molecular pharmacology · 2025Article
- Discovery of GluN2A subtype-selectiveActa pharmaceutica Sinica. B · 2024Review
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Development of a Dihydroquinoline-Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of theACS chemical neuroscience · 2023Article
- The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia.Genes · 2023Article
- Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators.Cellular and molecular neurobiology · 2023Review
- GluN2A-Selective NMDA Receptor Antagonists: Mimicking the U-Shaped Bioactive Conformation of TCN-201 by a [2.2]Paracyclophane System.ChemMedChem · 2022Article
- [2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists.ChemMedChem · 2021Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Study of Early Onset Schizophrenia: Associations ofLife (Basel, Switzerland) · 2021Article
- Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats.Pharmaceutics · 2021Article
- PTC-174, a positive allosteric modulator of NMDA receptors containing GluN2C or GluN2D subunits.Neuropharmacology · 2020Article
- Lupus autoantibodies act as positive allosteric modulators at GluN2A-containing NMDA receptors and impair spatial memory.Nature communications · 2020Article
- Dual action of amitriptyline on NMDA receptors: enhancement of Ca-dependent desensitization and trapping channel block.Scientific reports · 2019Article
- Functional and pharmacological properties of triheteromeric GluN1/2B/2D NMDA receptors.The Journal of physiology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GluN2A is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Physiological and genetic evidence implicate GluN2A-containing receptors in susceptibility to autism, schizophrenia, childhood epilepsy and neurodevelopmental disorders such as Rett Syndrome. However, GluN2A-selective pharmacological probes to explore the therapeutic potential of targeting these receptors have been lacking. Here we disclose a novel series of pyrazine-containing GluN2A antagonists exemplified by MPX-004 (5-(((3-chloro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)pyrazine-2-carboxamide) and MPX-007 (5-(((3-fluoro-4-fluorophenyl)sulfonamido)methyl)-N-((2-methylthiazol-5-yl)methyl)methylpyrazine-2-carboxamide). MPX-004 and MPX-007 inhibit GluN2A-containing NMDA receptors expressed in HEK cells with IC50s of 79 nM and 27 nM, respectively. In contrast, at concentrations that completely inhibited GluN2A activity these compounds have no inhibitory effect on GluN2B or GluN2D receptor-mediated responses in similar HEK cell-based assays. Potency and selectivity were confirmed in electrophysiology assays in Xenopus oocytes expressing GluN2A-D receptor subtypes. Maximal concentrations of MPX-004 and MPX-007 inhibited ~30% of the whole-cell current in rat pyramidal neurons in primary culture and MPX-004 inhibited ~60% of the total NMDA receptor-mediated EPSP in rat hippocampal slices. GluN2A-selectivity at native receptors was confirmed by the finding that MPX-004 had no inhibitory effect on NMDA receptor mediated synaptic currents in cortical slices from GRIN2A knock out mice. Thus, MPX-004 and MPX-007 offer highly selective pharmacological tools to probe GluN2A physiology and involvement in neuropsychiatric and developmental disorders.
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