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.

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.

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemical synthesis*
  • Alanine / pharmacology
  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Electrophysiology
  • Excitatory Amino Acid Agonists / chemical synthesis*
  • Excitatory Amino Acid Agonists / pharmacology
  • In Vitro Techniques
  • Ligands
  • Mice
  • Models, Molecular
  • Neurons / cytology
  • Neurons / drug effects
  • Oocytes / metabolism
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, AMPA / agonists*
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Recombinant Proteins / metabolism
  • Stereoisomerism
  • Xenopus laevis

Substances

  • CPW 399
  • Excitatory Amino Acid Agonists
  • Ligands
  • Pyrimidines
  • Pyrimidinones
  • Receptors, AMPA
  • Recombinant Proteins
  • Alanine