N-methyl-D-aspartate receptor containing GluN1 and GluN2B subunits (NMDA receptor (NR1/NR2B) or GluN1/GluN2B NMDA receptor)

The N-methyl-D-aspartate (NMDA) receptor containing GluN1 and GluN2B subunits is a subtype of the NMDA receptor, a ligand-gated ionotropic glutamate receptor critically involved in synaptic plasticity, learning, memory, and brain development[1][3][4][5]. It forms a heterotetramer typically consisting of two obligatory GluN1 (previously NR1) and two GluN2B (previously NR2B) subunits[1][4][5]. The receptor's unique gating requires co-agonist binding: glutamate binds to the GluN2B subunits, and glycine or D-serine binds to the GluN1 subunits[1][5]. Upon activation, the channel opens, allowing Ca²⁺ and Na⁺ influx and K⁺ efflux, with high calcium permeability and a characteristic magnesium block at resting membrane potentials[1][5]. The NR2B-containing NMDA receptors are especially abundant during early development and in specific brain regions and confer distinct functional and pharmacological properties. NR2B subunits influence receptor kinetics, localization, and protein interactions, and this subunit composition is implicated in multiple neurological and psychiatric disorders. Many drugs under investigation target the GluN1/GluN2B NMDA receptor for pain, neurodegenerative diseases, psychiatric disorders, and other CNS conditions[3][5]. Therapeutic modulation is complicated by risks such as interfering with physiological plasticity and cognitive function and causing side effects (such as dissociation or hallucinations), highlighting the need for subunit-selective targeting[3][5].

Other names

NMDA receptor NR1/NR2BNR1/NR2B NMDA receptorGluN1/GluN2B NMDA receptorNMDAR containing NR1 and NR2BN-methyl-D-aspartate receptor with GluN1 and GluN2B subunits

Uncompetitive antagonism (channel blockade, e.g., memantine) Allosteric inhibition (e.g., ifenprodil) Negative modulation at the NR2B subunit interface