N-methyl-D-aspartate receptor containing GluN2B subunit (NMDA receptor (GluN2B))

The N-methyl-D-aspartate receptor containing GluN2B subunit is a heteromeric, ligand-gated ion channel critical for excitatory synaptic transmission in the brain. The GluN2B-containing NMDA receptor is one of several receptor subtypes arising from variable subunit composition (two GluN1 and typically two GluN2, of which GluN2B is one variant, possibly joined by GluN2A or GluN3). This receptor permits calcium, sodium, and potassium ion flow upon simultaneous binding of glutamate and glycine or D-serine and appropriate postsynaptic depolarization to relieve its Mg^2+^ block. The GluN2B subunit governs several key properties including channel conductance, sensitivity to magnesium and zinc, kinetics of activation/deactivation, and allosteric modulator response (e.g., to ifenprodil). Functionally, this receptor is crucial for synaptic plasticity, learning, memory formation, and neurodevelopment; it is also strongly implicated in a range of neurological diseases. Selective antagonism of GluN2B NMDA receptors is being pursued as a therapeutic approach in neurodegenerative and neuropsychiatric diseases, but safety and efficacy remain major concerns due to the receptor’s essential physiological role.

Other names

NMDA receptor GluN2B subunitNR2B (historical)GluN2B (current IUPHAR nomenclature)NMDAR (with GluN2B composition)

Noncompetitive antagonism at the channel pore (memantine, ketamine, MK-801); Allosteric inhibition via the amino-terminal domain (Ifenprodil, Ro 25-6981); Channel blockage via voltage-dependent Mg^2+^ binding