title: Pharmacological characterization of some selected 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates and 3-hydroxyquinazoline-2,4-diones as (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic acid receptor antagonists.
abstract: In the present study, some selected, previously reported 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) and 3-hydroxy-quinazoline-2,4-diones (QZs), were evaluated for their affinity at the (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic acid (AMPA) receptor in the [(3)H]-6-cyano-7-nitroquinoxaline-2,3-dione ([(3)H]-CNQX) binding assay. Electrophysiological experiments were performed in oocytes expressing rat homomeric GluR3 subunits in order to assess the pharmacological profile of the tested compounds. The binding data, together with those regarding the functional activity, confirmed that most of the TQXs and QZs reported herein are potent AMPA receptor antagonists. When tested for their ability to prevent sound-induced seizures in DBA/2 mice, some of these derivatives showed anticonvulsant properties.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita' degli Studi di Firenze, Polo Scientifico, Fiorentino, Italy. daniela.catarzi@unifi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Catarzi
authors.forename: Ombretta
authors.initials: O
authors.lastname: Lenzi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Colotta
authors.forename: Flavia
authors.initials: F
authors.lastname: Varano
authors.forename: Daniela
authors.initials: D
authors.lastname: Poli
authors.forename: Guido
authors.initials: G
authors.lastname: Filacchioni
authors.forename: Kurt
authors.initials: K
authors.lastname: Lingenhöhl
authors.forename: Silvio
authors.initials: S
authors.lastname: Ofner
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
chemical_list: C494078:3-hydroxy-quinazoline-2,4-dione; D000927:Anticonvulsants; D011799:Quinazolines; D011810:Quinoxalines; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3