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Glutamate receptor ionotropic, NMDA (Glycine Site) (NMDA receptor (glycine site))

Target: NMDA receptor (glycine site)
Molecular classification: Receptor, Ion channel, Ligand-gated ion channel, Glutamate receptor, Ionotropic glutamate receptor

Overview

The NMDA receptor’s glycine site is an obligatory coagonist recognition pocket located on its essential GluN1/NR1 subunits. Occupancy by either endogenous ligands like glycine or D-serine enables full activation only when coupled with concurrent glutamate binding at adjacent sites. This dual-ligand gating underpins many key processes in CNS physiology while also providing pharmacological opportunities for therapeutic intervention targeting cognitive function or neuroprotection through modulation at this unique allosteric regulatory node within excitatory synapses.

Other names: NMDA receptor glycine siteNMDAR glycine siteGlycine binding site of NMDA receptorGluN1 glycine binding site

Mechanism of action

Modulation of NMDA receptor activity via the glycine co-agonist binding site.

Biological functions

Synaptic plasticityMemory formationExcitatory neurotransmissionLong-term potentiation (LTP)Long-term depression (LTD)Neuronal developmentSynapse formation

Disease associations

Neurodegenerative diseasePsychiatric disordersEpilepsyStrokeSchizophreniaDepressionAlzheimer's diseaseParkinson's disease

Safety considerations

Excitotoxicity (overactivation of NMDARs)Psychomimetic effects (with some NMDAR antagonists)Cognitive impairment (potential side effect of NMDAR modulation)Neurodevelopmental effects (in pediatric populations)

Interacting drugs

Glycine

5 more in the full profile.

Biomarkers

Extracellular glycine concentrationNMDAR subunit expression levelsCSF glycine levelsPlasma D-serine levels

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