Portal de Periódicos da CAPES

Discovery of a Novel and Highly Potent Noncompetitive AMPA Receptor Antagonist

2002; American Chemical Society; Volume: 46; Issue: 1 Linguagem: Inglês

10.1021/jm0210008

1520-4804

Rosaria Gitto, Maria Letizia Barreca, Laura De Luca, Giovambattista De Sarro, Guido Ferreri, Silvana Quartarone, Emilio Russo, Andrew Constanti, Alba Chimirri,

Coordination Chemistry and Organometallics

N-Acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were designed and synthesized as potential noncompetitive AMPA receptor antagonists on the basis of molecular modeling studies. Sound-induced seizure testing showed that this class of compounds possessed anticonvulsant properties. In particular, 10c was more potent than talampanel (2), a noncompetitive AMPA receptor antagonist currently being investigated in phase III trials as an antiepileptic agent. Furthermore, electrophysiological studies indicated that 10c was a highly effective noncompetitive-type modulator of the AMPA receptor.