N-methyl-D-aspartate receptor (NMDA receptor) (NMDA receptor (NMDAR))

The **N-methyl-D-aspartate receptor (NMDA receptor)** is a type of ionotropic glutamate receptor that forms a heterotetrameric ligand-gated ion channel, predominantly expressed in neurons of the central nervous system[1][2][3][4]. It plays a crucial role in **synaptic plasticity, learning, and memory** by mediating a Ca²⁺-permeable component of excitatory neurotransmission[3][4]. Activation requires the binding of the co-agonists **glutamate** and **glycine (or D-serine)**, along with relief of a voltage-dependent Mg²⁺ block, allowing intracellular influx of Ca²⁺, Na⁺, and K⁺ ions[3][4]. Structurally, NMDA receptors consist of two **GluN1** and two **GluN2 (A-D)** (or less commonly, **GluN3**) subunits, giving rise to several receptor subtypes with distinct pharmacological and signaling properties[2][3]. The NMDA receptor is therapeutically targeted in multiple neurologic and psychiatric disorders, but the modulation of its function is associated with both **efficacy and important safety risks**, such as cognitive impairment and potential for neurotoxicity or psychosis at extremes of antagonism or stimulation[4][3].

Other names

Neuronal NMDA receptor channelNMDA-type glutamate receptorGlutamate [NMDA] receptorNMDARGluN receptorGluN1/GluN2 receptorGluN1/GluN3 receptor

- Noncompetitive antagonism of the channel pore (e.g., ketamine, memantine, MK-801) - Competitive antagonism at the glutamate binding site (e.g., APV) - Glycine site antagonism (e.g., D-serine, glycine) - Allosteric modulation (e.g., ifenprodil, zinc, polyamines) - Open-channel block by Mg²⁺ (physiological modulation)