Glutamate ionotropic receptor NMDA type subunit 2B (GluN2B)

The N-methyl-D-aspartate (NMDA) receptor is a heterotetrameric ligand-gated ion channel essential for excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system (UniProt, 2024). NR2B-containing NMDA receptors, specifically those incorporating the Glutamate ionotropic receptor NMDA type subunit 2B, are predominantly expressed in the forebrain and play a critical role in modulating calcium influx and downstream signaling pathways associated with learning and memory (Mony et al., 2009). Dysregulation of these receptors is implicated in various neurological and psychiatric disorders, including major depressive disorder, Alzheimer's disease, and chronic pain (Wang et al., 2022). Unlike non-selective NMDA receptor antagonists, which often produce severe dissociative side effects, selective NR2B negative allosteric modulators offer a more targeted therapeutic window by specifically dampening overactive signaling (DrugBank, 2024). These receptors are also involved in excitotoxicity, where excessive glutamate release leads to neuronal death following ischemic events or in neurodegenerative conditions (StatPearls, 2023). Consequently, NR2B-containing receptors are high-priority targets for developing fast-acting antidepressants and neuroprotective agents.

Other names

NR2BGRIN2BN-methyl-D-aspartate receptor subunit 2BNMDA receptor type 2BN-methyl D-aspartate receptor subtype 2B

Negative allosteric modulation of the GluN1/GluN2B interface