Combined blockade of alpha3beta4 nicotinic acetylcholine receptors and GluR1 AMPA receptors in rats prevents kainate-induced tonic-clonic seizures.
Intramuscular injection of IEM-1754, a blocker of cerebral GluR1 AMPA receptors, in doses of 0.5-3.0 mg/kg decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate by 2.7-4 times. IEM-1678, an alpha3beta4 nicotinic acetylcholine receptor antagonist administered intramuscularly in a maximum dose of 3 mg/kg decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate by 2.3-2.7. IEM-1460 blocking both GluR1 AMPA receptors and alpha3beta4 nicotinic acetylcholine receptors, injected intramuscularly in doses of 0.5-3.0 mg/kg produced the maximum anticonvulsant activity and 8-fold decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate.
Serdyuk
S E
SE
Department of Neurophysiology, Institute of Experimental Medicine, Russian Academy of Medical Sciences, St Petersburg, Russia.
Gmiro
V E
VE
D000818:Animals; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D018733:Nicotinic Antagonists; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4; D007608:Kainic Acid