title: Combined blockade of NMDA and AMPA receptors prevents acute kainate seizures and chronic kainate lethality in rats.
abstract: 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%.
authors.affiliation: Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.
authors.forename: S E
authors.initials: SE
authors.lastname: Serdyuk
authors.forename: V E
authors.initials: VE
authors.lastname: Gmiro
authors.forename: O S
authors.initials: OS
authors.lastname: Veselkina
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007273:Injections, Intramuscular; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: C000595248:1-amino-6-(3,5-dimethyl-1-adamantylamine)hexane; D000588:Amines; D000927:Anticonvulsants; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016202:N-Methylaspartate; D000218:Adamantane; D007608:Kainic Acid; D008559:Memantine; D010433:Pentylenetetrazole