Aniracetam reverses the anticonvulsant action of NBQX and GYKI 52466 in DBA/2 mice.
Aniracetam (1-p-anisoyl-2-pyrrolidinone) selectively reverses the anticonvulsant activities of the non-NMDA receptor antagonists, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine.HCl) and, to a lesser extent, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline), without affecting the anticonvulsant activity of the competitive NMDA receptor antagonist, D(-)-CPPene, in DBA/2 mice. Pretreatment with aniracetam (50 nmol i.c.v., 15 min before drugs) increases the ED50 values (mumol/kg i.p., 15 min) for GYKI 52466-induced protection against sound-induced clonic seizures in DBA/2 mice 7 fold, from 20.1 (11.9-33.9) to 142 (91.7-219), and for NBQX-induced protection 2 fold, from 39.7 (33.8-46.7) to 85.6 (63.9-115), respectively. Aniracetam on its own (12.5-100 nmol i.c.v.) has no convulsant activity, but reverses the anticonvulsant effect of GYKI 52466 (60 mumol/kg i.p., 15 min) in a dose-dependent manner.
Chapman
A G
AG
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, UK.
al-Zubaidy
Z
Z
Meldrum
B S
BS
D000161:Acoustic Stimulation; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008811:Mice, Inbred DBA; D010879:Piperazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D011810:Quinoxalines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000517:prevention & control
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D010879:Piperazines; D011760:Pyrrolidinones; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; C065286:SDZ EAA 494; C036466:aniracetam