Discovery of a Novel and Highly Potent Noncompetitive AMPA Receptor Antagonist
Rosaria GittoDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KMaria Letizia BarrecaDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KLaura De LucaDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KGiovambattista De SarroDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KGuido FerreriDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KSilvana QuartaroneDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KEmilio RussoDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KAndrew ConstantiDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.KAlba ChimirriDipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy, Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia, Via T. Campanella, 88100 Catanzaro, Italy, and Department of Pharmacology, School of Pharmacy, University of London, 29/39, Brunswick Square, London, WC1N 1AX, U.K
2002en
ABI
Аннотация
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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