Over-additive anticonvulsant effect of memantine and NBQX in kindled rats.
We investigated the anticonvulsant and adverse effects of various dose combinations of the AMPA receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline) and the low-affinity, rapidly channel blocking NMDA receptor antagonist memantine in the kindling model of epilepsy. While memantine was ineffective when given alone, co-administration with NBQX markedly potentiated the increase in focal seizure threshold induced by NBQX alone. This synergistic (i.e. over-additive) interaction was seen at doses of both drugs which did not induce behavioural adverse effects. The data substantiate that combinations of AMPA and NMDA receptor antagonists provide a new strategy for the treatment of epileptic seizures.
Löscher
W
W
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Hönack
D
D
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects*; D008559:Memantine / Q000009:adverse effects / Q000494:pharmacology*; D011810:Quinoxalines / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D008559:Memantine