title: Comparative anticonvulsant activity of N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives in rodents.
abstract: The anticonvulsant activity of competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F)-quinoxaline (NBQX) and noncompetitive 2,3-benzodiazepines and tetrahydroisoquinolines (THIQs) AMPA/kainate receptor antagonists, was tested in different experimental seizure models and compared with diazepam, a conventional antiepileptic drug acting on GABAergic neurotransmission. In particular, the compounds were evaluated against audiogenic and maximal electroshock seizures (MES) test and pentetrazol (PTZ) seizures model, and all of them showed protective action. In addition, NBQX, 2,3-benzodiazepines and THIQs, but not diazepam, were also protective against clonic and tonic seizures and lethality induced by kainate, AMPA and ATPA, but were ineffective against NMDA-induced seizures. Only 2,3-benzodiazepines and some THIQs were able to affect 4-aminopyridine- and mercaptopropionic-acid-induced seizures. The duration of anticonvulsant action of 33 micromol/kg of some 2,3-benzodiazepines and THIQs was also investigated in DBA/2 mice, a strain genetically susceptible to audiogenic seizures, and it was observed that the derivative THIQ-10c, possessing an acetyl group at the N-2 and a chlorine atom on the C-1 phenyl ring, showed higher anticonvulsant activity and longer-lasting protective effects.
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, School of Medicine at Catanzaro, University of Catanzaro, Policlinico Mater Domini, Via T. Campanella, 115, 88100, Catanzaro, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferreri
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Pietro
authors.initials: P
authors.lastname: Gareri
authors.forename: Angela
authors.initials: A
authors.lastname: De Sarro
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D012640:Seizures / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline