[Bis-ammonium adamantane derivatives--novel modulators of polyamine binding sites].
Experiments on intact rats and mice showed that the polyamine agonist spermine and the bis-ammonium adamantyl-containing compounds IEM-1460 and IEM-1754 potentiate the NMDA induced analgesia and convulsions and eliminate the analgesic effects of nicotine and kainate. Arcain, a competitive polyamine antagonist, eliminated (at the same dose) the activating and blocking effects of spermine, IEM-1460 and IEM-1754. In small doses, IEM-1754 (similarly to arcain) removed the analgesic effect of NMDA. It is suggested that IEM-1460 (similarly to spermine) is a polyamine agonist, while IEM-1754 is an antagonist/agonist of the polyamine site of NMDA, AMPA/kainate, and nicotinic receptors. The potentiating activity of IEM-1460 is two orders higher as compared to that of spermine.
Department of Neuropharmacology, Russian Academy of Medical Sciences, St. Petersburg, Russia.
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D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001665:Binding Sites; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D013096:Spermine / Q000494:pharmacology
D000218:Adamantane; D001645:Biguanides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D013096:Spermine; C110702:IEM 1460; C092754:IEM 1754; C006624:arcaine