AMPA receptor potentiator

TAK-653 (osavampator, NBI-1065845) is an AMPA receptor positive allosteric modulator designed to amplify glutamate signaling only where glutamate is already being released — it binds the receptor's ligand-binding domain in a glutamate-dependent way and has virtually no agonist activity of its own, which in rats bought a 419-fold exposure margin against convulsions. In 24 healthy volunteers a single 6 mg dose raised motor-cortex excitability on TMS and produced a mild psychostimulant profile without euphoria or subjective drug effects. A phase 2 trial in depression reported a positive MADRS result, but only in a company press release; two phase 3 trials began in 2025.