Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and Kainate receptor (AMPAR/KAR)

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and Kainate receptors are subtypes of ionotropic glutamate receptors that mediate the majority of fast excitatory synaptic transmission in the brain (Traynelis et al., 2010). These receptors are composed of four subunits that form a central ion pore permeable to cations like sodium and potassium, playing a fundamental role in synaptic plasticity and memory formation. In the context of ketamine's pharmacology, these receptors are critical downstream mediators of its rapid antidepressant action. Ketamine-induced NMDA receptor blockade leads to a transient increase in glutamate that activates AMPA receptors, subsequently stimulating the release of brain-derived neurotrophic factor (BDNF) and activating the mTOR pathway to restore synaptic connectivity (Zanos et al., 2018). Consequently, these receptors are significant therapeutic targets for mood disorders, epilepsy, and neurodegenerative diseases.

Other names

Non-NMDA receptorsAMPA receptorsKainate receptorsGluAGluKIonotropic glutamate receptors

Ketamine indirectly enhances AMPA receptor signaling by blocking NMDA receptors on GABAergic interneurons, causing a glutamate surge that activates AMPA receptors and promotes synaptogenesis (Zanos et al., 2018). AMPA receptor antagonists like perampanel inhibit excitatory neurotransmission by binding to allosteric sites on the receptor (FDA, 2012).