Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR)

The Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is a primary ionotropic glutamate receptor that mediates the majority of fast excitatory synaptic transmission in the central nervous system [1, 2]. Structurally, it consists of tetrameric assemblies of four subunits (GluA1–GluA4) that form a ligand-gated cation channel primarily permeable to sodium and potassium ions [2, 3]. These receptors play a fundamental role in synaptic plasticity, particularly long-term potentiation and depression, which are essential for learning and memory processes [3, 4]. Dysregulation or overactivation of AMPA receptors is heavily implicated in excitotoxicity, leading to neuronal damage in conditions such as epilepsy, stroke, and amyotrophic lateral sclerosis (ALS) [1, 5]. Therapeutically, non-competitive antagonists like perampanel are utilized to manage seizures by reducing excessive excitatory signaling, while positive allosteric modulators (ampakines) have been investigated for potential cognitive enhancement [5, 6]. However, the therapeutic window is often limited by side effects such as sedation, motor coordination issues, and significant neuropsychiatric behavioral changes [6].

Other names

AMPA-type glutamate receptorAMPARGluRGluAIonotropic glutamate receptor 1-4Quisqualate receptor

Non-competitive antagonism, competitive antagonism, positive allosteric modulation, and channel pore blocking.