Characterization of the 1<i>H</i>-Cyclopentapyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione Derivative (S)-CPW399 as a Novel, Potent, and Subtype-Selective AMPA Receptor Full Agonist with Partial Desensitization Properties

Abstract

(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca(2+)](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.