ArticleThe Journal of pharmacology and experimental therapeutics2010
Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Development of a Dihydroquinoline-Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of theACS chemical neuroscience · 2023Article
- Histamine HCellular and molecular neurobiology · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Activation of CREB-mediated autophagy by thioperamide ameliorates β-amyloid pathology and cognition in Alzheimer's disease.Aging cell · 2021Article
- PTC-174, a positive allosteric modulator of NMDA receptors containing GluN2C or GluN2D subunits.Neuropharmacology · 2020Article
- Biased modulators of NMDA receptors control channel opening and ion selectivity.Nature chemical biology · 2020Article
- A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate.Journal of visualized experiments : JoVE · 2018Article
- A Novel Negative Allosteric Modulator Selective for GluN2C/2D-Containing NMDA Receptors Inhibits Synaptic Transmission in Hippocampal Interneurons.ACS chemical neuroscience · 2018Article
- The Bioactive Protein-Ligand Conformation of GluN2C-Selective Positive Allosteric Modulators Bound to the NMDA Receptor.Molecular pharmacology · 2018Article
- A NMDA-receptor calcium influx assay sensitive to stimulation by glutamate and glycine/D-serine.Scientific reports · 2017Article
- NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy.Scientific reports · 2017Article
- MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit.PloS one · 2016Article
- A novel class of negative allosteric modulators of NMDA receptor function.Bioorganic & medicinal chemistry letters · 2015Article
- A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.Molecular neurobiology · 2015Review
- International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.Pharmacological reviews · 2015Review
- Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators.Journal of medicinal chemistry · 2014Article
- Synthesis and structure activity relationship of tetrahydroisoquinoline-based potentiators of GluN2C and GluN2D containing N-methyl-D-aspartate receptors.Journal of medicinal chemistry · 2013Article
- Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.Current topics in medicinal chemistry · 2013Review
- Molecular pharmacology of human NMDA receptors.Neurochemistry international · 2012Article
- Mapping the binding of GluN2B-selective N-methyl-D-aspartate receptor negative allosteric modulators.Molecular pharmacology · 2012Article
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Authors and funding
19 authors at 1 institution in 1 country.
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Abstract
N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate a slow, Ca(2+)-permeable component of excitatory synaptic transmission in the central nervous system and play a pivotal role in synaptic plasticity, neuronal development, and several neurological diseases. We describe a fluorescence-based assay that measures NMDA receptor-mediated changes in intracellular calcium in a BHK-21 cell line stably expressing NMDA receptor NR2D with NR1 under the control of a tetracycline-inducible promoter (Tet-On). The assay selectively identifies allosteric modulators by using supramaximal concentrations of glutamate and glycine to minimize detection of competitive antagonists. The assay is validated by successfully identifying known noncompetitive, but not competitive NMDA receptor antagonists among 1800 screened compounds from two small focused libraries, including the commercially available library of pharmacologically active compounds. Hits from the primary screen are validated through a secondary screen that used two-electrode voltage-clamp recordings on recombinant NMDA receptors expressed in Xenopus laevis oocytes. This strategy identified several novel modulators of NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine H3 receptor ligand showed submicromolar potency at NR1/NR2B NMDA receptors, which raises the possibility that compounds can be developed that act with high potency on both glutamate and histamine receptor systems simultaneously. Furthermore, it is possible that some actions attributed to histamine H3 receptor inhibition in vivo may also involve NMDA receptor antagonism.
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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.