Glutamate receptor ionotropic, AMPA type (AMPA receptor) (AMPAR)

The AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) is a subtype of ionotropic glutamate receptor that mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system (StatPearls, NBK541033). These receptors are tetrameric assemblies of four subunits (GluA1-GluA4) that form a ligand-gated cation channel (UniProt, P42261). The term "2,3-benzodiazepine receptor" specifically refers to a unique allosteric binding site located within the transmembrane domain of the AMPA receptor, distinct from the glutamate binding site and the 1,4-benzodiazepine site on GABA-A receptors (PubMed, 2555157). Non-competitive antagonists like perampanel and GYKI 52466 bind to this site to inhibit channel opening, thereby reducing neuronal hyperexcitability (PubChem, CID 10096344). Because overactivation of AMPA receptors is linked to seizure activity and excitotoxic neuronal death, this target is clinically significant for treating epilepsy and exploring neuroprotective therapies for conditions like ALS and stroke (PubMed, 10774917). Therapeutic challenges include managing central nervous system side effects such as dizziness, ataxia, and behavioral changes like aggression (FDA, Fycompa Label).

Other names

2,3-benzodiazepine receptorAMPA receptorGluAGluRQuisqualate receptorAlpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

Non-competitive allosteric antagonism of the AMPA receptor at the 2,3-benzodiazepine binding site.