Combined Blockade of AMPA and NMDA Receptors Produces Maximal Suppression of the Development of Corasol Kindling in Rats

Abstract

Chronic enteral administration of the standard antiepileptic drug sodium valproate at a dose of 200 mg/kg suppressed the development of generalized clonic-tonic corasol-kindled convulsions in 100% of rats but prevented kindled clonic convulsions in only 57%. This dose of sodium valproate decreased the mean severity of corasol-kindled convulsions by a factor of 1.7. Chronic enteral administration of IEM-2121, which induces combined blockade of AMPA and NMDA glutamate receptors, and IEM-1676, which blocks AMPA and NMDA receptors, as well as n-cholinoreceptors, given at doses of 10 and 20 mg/kg, respectively, had greater anticonvulsive activity than sodium valproate, as they decreased the mean severity of corasol-kindled convulsions by factors of 2.4–2.7 as compared with controls and prevented kindled clonic convulsions in 87% of rats. Combined blockade of AMPA and NMDA receptors and, possibly, n-cholinoreceptors, produced the greatest suppression of epileptogenesis in relation to both clonic and clonic-tonic corasol-kindled convulsions.