Glutamate ionotropic receptor NMDA type subunit 2B (GluN2B) (GluN2B)

The Glutamate ionotropic receptor NMDA type subunit 2B (GluN2B) is a key regulatory subunit of the N-methyl-D-aspartate (NMDA) receptor, a ligand-gated ion channel essential for excitatory neurotransmission in the mammalian brain (UniProt: Q13224; NCBI Gene: 2904). Predominantly expressed in the forebrain, GluN2B-containing receptors are critical mediators of synaptic plasticity, long-term potentiation, and cognitive functions such as learning and memory (PubMed: PMC2699664). Pathological overactivation or dysfunction of these receptors is linked to excitotoxicity and various disorders, including major depressive disorder, chronic pain, and neurodegenerative diseases like Alzheimer's and Parkinson's (PubMed: 24930970). Pharmacologically, GluN2B is a highly sought-after target because its selective modulation offers the potential for therapeutic efficacy—particularly as a rapid-acting antidepressant—without the severe psychotomimetic side effects associated with non-selective NMDA antagonists like ketamine (PubMed: 31130854). Drugs targeting this subunit, such as ifenprodil and its derivatives, typically act as negative allosteric modulators that decrease the channel's open probability in a state-dependent manner (PubMed: 12465331).

Other names

NR2BGRIN2BN-methyl D-aspartate receptor subtype 2BGlutamate receptor ionotropic, NMDA 2BhNR2B

Negative allosteric modulation of the NMDA receptor complex, specifically targeting the GluN2B subunit to reduce calcium conductance without complete channel blockade.