The non-N-methyl-D-aspartate receptor antagonists, GYKI 52466 and NBQX are anticonvulsant in two animal models of reflex epilepsy.
The effect of i.p. or i.v. administration of the non-N-methyl-D-aspartate antagonists, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepin e.HCl, molecular weight 330) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline, molecular weight 342) on sound-induced seizures in rats and photically induced myoclonus in baboons was studied. In both species an anticonvulsant effect occurred 15-60 min after administration of GYKI 52466 or NBQX. The ED50 value for clonic seizure suppression for GYKI 52466 at 30 min was 39 (rats, i.p.) and at 15 min was 13 (Papio papio, i.v.) mumol kg-1 and for NBQX at 30 min was 40 (rats, i.p.) and at 15 min approximately 10 (Papio papio, i.v.) mumol kg-1. Side effects were not observed in rats; apparent side effects in baboons probably arose from drug formulation. The anticonvulsant actions of GYKI 52466 and NBQX suggest a possible role for non-NMDA antagonists in the therapy of epilepsy.
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, U.K.
S E
SE
Smith
N
N
Dürmüller
B S
BS
Meldrum
D000161:Acoustic Stimulation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004831:Epilepsies, Myoclonic / Q000517:prevention & control; D004827:Epilepsy / Q000235:genetics / Q000517:prevention & control*; D004830:Epilepsy, Tonic-Clonic / Q000517:prevention & control; D005260:Female; D008297:Male; D010215:Papio; D010775:Photic Stimulation; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D011810:Quinoxalines; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines