Search

Adamantane-containing glutamate blocker IEM-1913 (1-amino-4-(1-adamantane-amino)-butane dihydrochloride) equals to memantine in antiparkinsonian potency, but surpasses it in anticonvulsive, antidepressant, and analgesic activities. Moreover, its use is less toxic and safer. IEM-1913 produces significant pharmacological effects at a wide concentration diapason (0.03-1.00 mg/kg), while memantine is effective within a narrow range only (15-20 mg/kg). High pharmacological efficacy and low toxicity of IEM-1913 can be explained by the fact that in contrast to monocationic selective NMDA antagonist memantine, the dicationic glutamate blocker IEM-1913 produces a combined block of cerebral NMDA and AMPA receptors.

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%.