The anticonvulsant effect of the non-NMDA antagonists, NBQX and GYKI 52466, in mice

Abstract

The excitatory amino acid antagonists, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline) and GYKI 52466 (l-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2,3-benzodiazepine) that act on non-NMDA receptors, provide potent anticonvulsant protection against AMPA ((RS)-α-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 ED 50 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) μmol/kg, respectively. The ED 50 values at 15 min for the protection against sound-induced seizures in DBA/2 mice are 31.3 (24.9–39.4) μmol/kg (NBQX i.p.), 37.8 (21.2–67.4) μmol/kg (NBQX i.v.) and 13.7 (11.5–16.5) μmol/kg (GYKI 52466, i.p.). In DBA/2 mice the therapeutic index (ratio of ED 50 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.).