title: Novel potent anticonvulsant agent containing a tetrahydroisoquinoline skeleton.
abstract: In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure-activity relationships. All derivatives were evaluated against audiogenic seizures in DBA/2 mice, and the 1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl) derivative (26) showed the highest activity with a potency comparable to that of talampanel, the only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. rgitto@pharma.unime.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pagano
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C514070:1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl)-1,2,3,4-tetrahydroisoquinoline; D000927:Anticonvulsants; D007546:Isoquinolines; D010880:Piperidines; D018091:Receptors, AMPA; D044005:Tetrahydroisoquinolines