AMPA receptor positive allosteric modulator

[1] AMPAR PAMs have cognition- and memory-enhancing and antidepressant-like effects in preclinical models.

[3] 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).

[2] The AMPAR is one of the most highly expressed receptors in the brain, and is responsible for the majority of fast excitatory amino acid neurotransmission in the central nervous system (CNS).

[4][1] For this reason, doubt has been cast on the feasibility of AMPAR activators for use in medicine.

[6] There are several major chemical classes of AMPAR PAMs:[8][4] These classes have divergent properties, including allosteric site specificity, potency, impact (i.e., low versus high), and selectivity for AMPAR populations composed of different subunits.