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Updated: Sep 28, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Discovery of a novel and highly potent noncompetitive AMPA receptor antagonist
Rosaria Gitto1, Maria Letizia Barreca, Laura De Luca
1Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
Abstract:
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.
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