Chronic oral administration of the selective AMPA receptor blocker IEM-1676 and the combined NMDA and AMPA receptor blocker IEM-1913 decreased the severity of convulsions kindled by corasol (pentylenetetrazole) and also the number of rats with full kindling by 20–40% more than the standard antiepileptic sodium valproate and the selective NMDA receptor blocker memantine. IEM-1913 and IEM-1676 induced anticonvulsant effects over wide dose ranges, of 0.03–1 and 3–40 mg/kg, respectively, while memantine and sodium valproate were effective only in narrow dose ranges, of 12–20 and 100–200 mg/kg, respectively. Sodium valproate, memantine, and IEM-1676 had low therapeutic indexes (TD50/ED50), of 1.7, 2.0, and 8.0, respectively, evidencing the high chronic toxicity and low safety of these agents. IEM-1913 had a therapeutic index of 1600, which is evidence of low toxicity and high safety in the chronic use of IEM-1913. Thus, the selective blockade of AMPA receptors induced by IEM-1676 is sufficient to achieve a maximum anticonvulsant effect in rats with corasol kindling, though only combined blockade of NMDA and AMPA receptors provide both the maximal anticonvulsant activity and the safety of using IEM-1913 over a wide range of effective doses.