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.
Gmiro
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Department of Neuropharmacology, Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia. g2119@online.ru
Serdyuk
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D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001645:Biguanides / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*
D001645:Biguanides; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C006624:arcaine; D008559:Memantine; D010433:Pentylenetetrazole