N-methyl-D-aspartate receptor subunit 2B (NR2B) (NR2B)

The N-methyl-D-aspartate receptor subunit 2B (NR2B), also known as GluN2B, is a critical component of heterotetrameric NMDA receptor complexes, which are ligand-gated ion channels essential for excitatory neurotransmission and synaptic plasticity in the mammalian brain (Paoletti et al., 2013). These receptors are primarily localized in the forebrain and are distinguished by their high calcium permeability and slow deactivation kinetics, playing a pivotal role in learning and memory (Wang et al., 2014). In pathological states, the overactivation of NR2B-containing receptors, particularly those at extrasynaptic sites, is a major driver of excitotoxicity, contributing to neuronal death in stroke, traumatic brain injury, and neurodegenerative diseases such as Alzheimer's and Parkinson's (Ge et al., 2020). Conversely, NR2B hypofunction is linked to neurodevelopmental disorders like autism and psychiatric conditions such as schizophrenia (Liu et al., 2017). Pharmacologically, NR2B-containing complexes are targeted by negative allosteric modulators (NAMs) like ifenprodil and traxoprodil, which offer a more favorable safety profile than non-selective NMDA antagonists by selectively inhibiting overactive receptors while preserving basic synaptic function (Menniti et al., 1998). These agents have been investigated for their potential in treating treatment-resistant depression, chronic pain, and providing neuroprotection (Preskorn et al., 2008).

Other names

GluN2BGRIN2BGlutamate receptor ionotropic, NMDA 2BGlutamate [NMDA] receptor subunit epsilon-2N-methyl D-aspartate receptor subtype 2B

Negative allosteric modulation