AMPA receptor positive allosteric modulator

AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the AMPA receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system.

AMPAR PAMs have cognition- and memory-enhancing and antidepressant-like effects in preclinical models, and have potential medical applications in the treatment of cognitive impairment (e.g., cognitive symptoms in schizophrenia, mild cognitive impairment), dementia (e.g., Alzheimer's disease), depression, and for other indications. They can broadly be divided into low-impact and high-impact potentiators, with high-impact potentiators able to produce comparatively more robust increases in AMPAR activation. However, high-impact AMPAR PAMs can cause motor coordination disruptions, convulsions, and neurotoxicity at sufficiently high doses, similarly to orthosteric AMPAR activators (i.e., active/glutamate site agonists).