The anticonvulsant effect of the non-NMDA antagonists, NBQX and GYKI 52466, in mice.
The excitatory amino acid antagonists, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline) and GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine) that act on non-NMDA receptors, provide potent anticonvulsant protection against AMPA [RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-induced seizures in Swiss mice and against sound-induced seizures in seizure-susceptible DBA/2 mice. Maximal anticonvulsant protection is observed 5-30 min after the i.p. administration of NBQX and 5-15 min after the i.p. administration of GYKI 52466 in DBA/2 mice. The ED50 values for the protection against AMPA-induced seizures by NBQX (30 min, i.p.) and GYKI 52466 (15 min, i.p.) are 23.6 (11.6-48.0) and 18.5 (11.5-29.5) mumol/kg, respectively. The ED50 values at 15 min for the protection against sound-induced seizures in DBA/2 mice are 31.3 (24.9-39.4) mumol/kg (NBQX, i.p.), 37.8 (21.2-67.4) mumol/kg (NBQX, i.v.) and 13.7 (11.5-16.5) mumol/kg (GYKI 52466, i.p.). In DBA/2 mice the therapeutic index (ratio of ED50 values for impaired rotarod performance and anticonvulsant action) is 6.6 for NBQX (15 and 30 min, i.p.) and 2.0 for GYKI 52466 (15 min, i.p.).
Chapman
A G
AG
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, U.K.
Smith
S E
SE
Meldrum
B S
BS
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D004856:Postural Balance / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D011810:Quinoxalines; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid