AMPA-type ionotropic glutamate receptor (AMPA receptor (AMPAR))

The **AMPA-type ionotropic glutamate receptor** is a tetrameric ligand-gated ion channel found abundantly in the central nervous system, primarily mediating fast excitatory synaptic transmission through binding of the major neurotransmitter glutamate[1][5][6]. AMPARs are composed of various combinations of four subunits (GluA1–GluA4, encoded by GRIA1–4), each having an extracellular ligand-binding domain, multiple transmembrane domains forming an ion pore, and an intracellular tail[1][2][6]. Upon glutamate binding, the receptor opens to allow cation influx (mainly Na⁺ and some Ca²⁺), which contributes to the rapid excitation of postsynaptic neurons and underlies processes such as synaptic plasticity, long-term potentiation (LTP), learning, and memory[5][6]. Dysfunction or overstimulation of AMPA receptors is implicated in several diseases, including epilepsy, neurodegenerative disorders, and psychiatric conditions, making AMPAR a validated and clinically exploited therapeutic target, particularly for antiepileptic drugs such as perampanel[3][7][9]. Multiple modulatory drugs, including antagonists and positive allosteric modulators, act on different sites of the receptor to adjust its function for therapeutic purposes[5][7]. AMPAR function is also finely tuned by auxiliary subunits such as TARPs and cornichons, which further diversify physiological and pharmacological properties[2][8].

Other names

AMPA receptorα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptorGluA receptorIonotropic glutamate receptor AMPA-typeGlutamate receptor ionotropic, AMPA

Competitive antagonism (inhibiting glutamate binding); Non-competitive antagonism (allosteric inhibition, e.g., perampanel); Positive allosteric modulation (e.g., AMPAkines enhance receptor response); Negative allosteric modulation