Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate ionotropic glutamate receptors (Non-NMDA receptors) (AMPAR/KAR)

AMPA and kainate receptors are two of the three main classes of ionotropic glutamate receptors (iGluRs) in the central nervous system, collectively often referred to as non-NMDA receptors [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633012/]. They are tetrameric ligand-gated ion channels that mediate the majority of fast excitatory synaptic transmission by allowing the influx of cations, primarily sodium and potassium, upon glutamate binding [Wikipedia, https://en.wikipedia.org/wiki/AMPA_receptor]. While AMPA receptors (composed of GluA1-4 subunits) are the primary drivers of rapid postsynaptic depolarization and are essential for synaptic plasticity, kainate receptors (composed of GluK1-5 subunits) play a more modulatory role, influencing both presynaptic neurotransmitter release and postsynaptic excitability [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633012/]. Dysregulation of these receptors is implicated in a wide range of neurological and psychiatric conditions, including epilepsy, stroke-induced excitotoxicity, and neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135178/]. Pharmacological targeting of these receptors includes the use of non-competitive antagonists like perampanel for seizure control and the development of positive allosteric modulators (ampakines) as potential cognitive enhancers [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633012/]. However, therapeutic development is challenged by the need for subtype selectivity to avoid side effects such as convulsions or excessive sedation [MDPI, https://www.mdpi.com/1424-8247/17/7/884].

Other names

Non-NMDA receptorsQuisqualate receptorsAMPAR/KARGlutamate ionotropic receptors AMPA/kainate type

Drugs targeting these receptors primarily act as non-competitive or competitive antagonists to reduce excessive excitatory signaling in conditions like epilepsy, or as positive allosteric modulators (PAMs) to enhance synaptic transmission and cognitive function [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633012/].