Combined blockade of NMDA and AMPA receptors prevents acute kainate seizures and chronic kainate lethality in rats.

Single intramuscular injection of selective of NMDA receptor blocker memantine in the maximum dose of 20 mg/kg prevented the development of acute generalized tonic-clonic kainate seizures in 60% rats, but did not alleviate clonic kainate seizures and prevented chronic kainate lethality in only 30% rats. Intramuscular injection of NBQX, a selective blocker of AMPA receptors (10 mg/kg), produced more pronounced anticonvulsant and neuroprotective effects: it prevented generalized kainate seizures and chronic kainate lethality in 100 and 80% rats, respectively. However, even the high dose of NBQX prevented the clonic kainate seizures only in 30% rats. The intramuscular injection of novel agent IEM-2121 (0.03-1.00 mg/kg) known to block both AMPA and NMDA receptors, prevented the clonic kainate seizures only in 50-70%, although it precluded the chronic kainate lethality in 100%.