N-methyl-D-aspartate receptor subunit 2B (GluN2B) (GluN2B)

The N-methyl-D-aspartate (NMDA) receptor is a heterotetrameric ligand-gated ion channel essential for excitatory neurotransmission and synaptic plasticity in the central nervous system (StatPearls, 2023). Subtypes containing the GluN2B subunit, encoded by the GRIN2B gene, are primarily expressed in the forebrain and are critical regulators of calcium influx, which is vital for long-term potentiation and memory formation (UniProt, Q13224). Dysregulation of GluN2B-containing receptors is heavily implicated in the pathophysiology of major depressive disorder, chronic pain, and neurodegenerative diseases like Alzheimer's, often due to glutamate-mediated excitotoxicity (PubMed, PMID: 30107114). Pharmacological targeting of these specific subtypes, particularly through negative allosteric modulators (NAMs), aims to provide therapeutic benefits such as rapid antidepressant effects while minimizing the severe dissociative side effects associated with non-selective NMDA antagonists like ketamine (PubMed, PMID: 25563902). These drugs typically bind to the interface of the GluN1 and GluN2B subunits, reducing the channel's open probability in a state-dependent manner to normalize glutamatergic signaling.

Other names

Glutamate ionotropic receptor NMDA type subunit 2BNR2BGRIN2BNMDAR2BGlutamate receptor subunit epsilon-2hNR2B

Negative allosteric modulation of the GluN2B subunit to inhibit ion channel activity and reduce calcium influx; non-competitive antagonism.