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

The glutamate receptor ionotropic AMPA type (AMPA receptor, AMPAR) is a ligand-gated ion channel that mediates fast excitatory synaptic transmission in the central nervous system[3][2]. It is a tetrameric protein complex composed of four subunits (GluA1–GluA4, encoded by GRIA1–4), forming a central ion-conducting pore permeable primarily to sodium (Na⁺) and, depending on subunit composition and RNA editing, sometimes calcium (Ca²⁺)[1][2][3]. AMPA receptors are activated by glutamate, the main excitatory neurotransmitter in the brain, and play a vital role in synaptic plasticity, learning, and memory. The structural complexity includes an extracellular amino-terminal domain (NTD), ligand-binding domain (LBD), transmembrane domain (forming the channel), and cytoplasmic C-terminal domain (CTD). Auxiliary proteins such as TARPs and CNIHs modulate AMPAR function, trafficking, and gating[6][4]. AMPAR dysfunction or dysregulation is implicated in neurodegenerative diseases, epilepsy, ischemia, and some psychiatric disorders[3]. Pharmacologically, it is an established target for antiepileptic and neuroprotective drugs, but modulating AMPAR activity is challenging due to its fundamental physiological role and the risk of adverse cognitive and neuropsychiatric effects[2].

Other names

AMPA receptorAMPARα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptorGluA1/GluA2/GluA3/GluA4 (for subtypes)GluR1-GluR4 (historical names)Ionotropic glutamate receptor AMPA type

Antagonists: block glutamate-mediated current through the AMPA receptor ion channel, reducing excitatory neurotransmission (e.g., perampanel is a non-competitive antagonist)[2][5] Positive allosteric modulators: enhance synaptic response by stabilizing the active (open) state