[Blockade of the alpha3alpha4 N-cholinoreceptors and GluR1 AMPA receptors eliminates clonic-tonic nicotinic and kainate seizures].
Monoammonium N-alkyl derivative of decylamine (IEM-1678), which blocks alpha3beta4 N-cholinoreceptors (but does not block GluR1 AMPA receptors), in doses of 1.0 - 3.0 mg/kg produces a 4-fold decrease in the frequency and lethality of nicotinic clonic-tonic seizures. However, even in the maximum dose of 3 mg/kg, IEM-1678 only slightly decreases kainate clonic-tonic seizures. Bis-ammonium compound IEM-1460 (containing adamantyl radical), which blocks both GluR1 AMPA receptors and alpha3beta4 N-cholinoreceptors, in a range of doses 0.1 - 3 mg/kg produces a 5- to 8-fold decrease in the frequency and virtually completely eliminates lethality of both clonic-tonic nicotinic and kainate seizures. Hence, the complete elimination of generalized kainate and nicotinic seizures requires combined blockade GluR1 AMPA and alpha3beta4 N-cholinoreceptors.
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D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D007608:Kainic Acid; D008297:Male; D009538:Nicotine; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D000218:Adamantane; D007608:Kainic Acid; D009538:Nicotine; D018733:Nicotinic Antagonists; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic; C090123:IEM 1078; C110702:IEM 1460; C403530:nicotinic receptor alpha3beta4