Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia.

Intramuscular injection of selective NMDA receptor antagonists memantine and arcaine 4-fold decreased the incidence of pentylenetetrazole-induced generalized tonic-clonic seizures in rats, while the incidence of clonic seizures decreased by 1.2-1.3 times. Memantine and arcaine are characterized by low therapeutic index, i.e. induced ataxia in rats in doses exceeding the effective anticonvulsant dose by only 3.5-10 times. Intramuscular injection of IEM-1913 (combined blockade of NMDA and AMPA receptors in the brain) decreased the incidence of pentylenetetrazole-induced clonic and tonic-clonic seizures in rats by 4-8 times. The therapeutic index of IEM-1913 surpassed that of memantine and arcaine by 200-600 times.