[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.
AuthorsS E Serdiuk, V E Gmiro
JournalEksperimental'naia i klinicheskaia farmakologiia (Eksp Klin Farmakol) 2008 Jul-Aug Vol. 71 Issue 4 Pg. 14-7 ISSN: 0869-2092 [Print] Russia (Federation)
PMID18819435 (Publication Type: English Abstract, Journal Article)
Chemical References
  • IEM 1078
  • IEM 1460
  • Nicotinic Antagonists
  • Quaternary Ammonium Compounds
  • Receptors, AMPA
  • Receptors, Nicotinic
  • glutamate receptor ionotropic, AMPA 1
  • nicotinic receptor alpha3beta4
  • Nicotine
  • Adamantane
  • Kainic Acid
  • Adamantane (analogs & derivatives, pharmacology)
  • Animals
  • Kainic Acid
  • Male
  • Nicotine
  • Nicotinic Antagonists (pharmacology)
  • Quaternary Ammonium Compounds (pharmacology)
  • Rats
  • Receptors, AMPA (antagonists & inhibitors)
  • Receptors, Nicotinic (metabolism)
  • Seizures (chemically induced, drug therapy)

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