Comparative anticonvulsant activity of some 2,3-benzodiazepine derivatives in rodents.
The anticonvulsant activities of some 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)/kainate receptor antagonists, noncompetitive (2,3-benzodiazepines) and a competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX), were compared in different experimental seizure models. In particular, compounds were evaluated against audiogenic seizure in DBA/2 mice, maximal electroshock seizure (MES) test and various chemoconvulsant models; both groups showed a protective action against audiogenic seizure, MES- and pentylenetetrazole (PTZ)-induced seizures. All 2,3-benzodiazepines were also protective against clonic and tonic seizures and lethality induced by 4-aminopyridine, kainate, AMPA and 3-mercaptopropionic acid but were ineffective against NMDA-induced seizures. NBQX was unable to affect 4-aminopyridine-, mercaptopropionic acid- and NMDA-induced seizures. The duration of anticonvulsant action of 33 micromol/kg of some 2,3-benzodiazepine in DBA/2 mice, genetically susceptible to audiogenic seizures, was also investigated. The derivatives possessing a thiocarbonyl group at the C-4 position of heptatomic ring showed higher anticonvulsant activities and longer lasting protective effects. We conclude that all 2,3-benzodiazepines studied are effective against various models of experimental epilepsy and the presence of thiocarbonyl groups at the C-4 position of heptatomic ring is able to increase the anticonvulsant effect of these compounds.
De Sarro
Giovambattista
G
Department of Experimental and Clinical Medicine, School of Medicine at Catanzaro, Policlinico Mater Domini, Via T. Campanella, 115, 88100, Catanzaro, Italy. desarro@unicz.it
Ferreri
Guido
G
Gareri
Pietro
P
Russo
Emilio
E
De Sarro
Angela
A
Gitto
Rosaria
R
Chimirri
Alba
A
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000737:chemistry* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods; D020195:Epilepsy, Reflex / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
D000927:Anticonvulsants; D001569:Benzodiazepines