Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties

  • J Med Chem. 2001 Dec 20;44(26):4501-4. doi: 10.1021/jm015552m.
G Campiani  1 ,  E Morelli ,  V Nacci ,  C Fattorusso ,  A Ramunno ,  E Novellino ,  J Greenwood ,  T Liljefors ,  R Griffiths ,  C Sinclair ,  H Reavy ,  A S Kristensen ,  D S Pickering ,  A Schousboe ,  A Cagnotto ,  E Fumagalli ,  T Mennini
Affiliations
  • 1. Dipartimento Farmaco Chimico Tecnologico (DFCT), Universita' degli Studi di Siena, via Aldo Moro, 53100 Siena, Italy. [email protected]
PMID: 11741469 DOI: 10.1021/jm015552m
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.