Glutamate ionotropic receptor AMPA type (AMPAR)

The Glutamate ionotropic receptor AMPA type (AMPAR) is a critical ligand-gated ion channel that mediates the majority of fast excitatory synaptic transmission in the central nervous system [2, 10]. Composed of four subunits (GluA1-4), these receptors are essential for synaptic plasticity, including long-term potentiation and depression, which serve as the cellular basis for learning and memory [2, 22, 32]. Dysregulation of AMPAR function is implicated in a wide range of neurological and psychiatric disorders, such as epilepsy, where overactivation leads to seizures, and neurodegenerative diseases like Alzheimer's and ALS, where excitotoxicity or synaptic loss occurs [1, 8, 16]. Pharmacological targeting of AMPARs includes antagonists like perampanel for epilepsy and positive allosteric modulators (ampakines) being explored for cognitive enhancement and depression [5, 12, 25]. Despite their therapeutic potential, targeting AMPARs presents challenges due to their ubiquitous expression and the risk of side effects like sedation or pro-convulsant activity [5, 7, 26].

Other names

AMPA receptorGluRGRIAQuisqualate receptorAlpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

Drugs targeting the AMPA receptor primarily act through non-competitive antagonism (allosteric inhibition), competitive antagonism, or positive allosteric modulation (PAM) to either decrease or increase the frequency and duration of ion channel opening in response to glutamate binding [1, 5, 19].