[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.