[The search for selective blockers of NMDA and AMPA/kainate receptors in a series of bis-ammonium compounds with adamantyl radicals].
Two groups of substances capable of selectively blocking the NMDA and AMPA/kainate receptors in experiments on intact animals were found in a series of bis-ammonium compounds with adamantyl radicals. The selective NMDA receptor blockers (IEM-1754, IEM-1755, IEM-1752), as well as the reference agents MK-801 and memantine, produced anticonvulsant, anti-ischemic, and antihypoxant effects and prevented the loss of experimental animals from toxic doses of NMDA. The selective AMPA/kainate receptor blockers (IEM-1553, IEM-1751, IEM-1592, and DNQX)) also produced the anticonvulsant, anti-ischemic, and antihypoxant effects, but did not prevent from the loss of animals caused by the toxic doses of NMDA. The maximum activity was observed for IEM-1754, the activity of which exceeded that of MK-801 (by a factor of 5-10) and memantine (by a factor of 300-800) in all the test objects.
Gmiro
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Anichkov Department of Neuropharmacology, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Serdiuk
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D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000139:chemically induced / Q000188:drug therapy; D003292:Convulsants; D004353:Drug Evaluation, Preclinical; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D000860:Hypoxia / Q000188:drug therapy; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010433:Pentylenetetrazole; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D012977:Sodium Nitrite
D000218:Adamantane; D000927:Anticonvulsants; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D010433:Pentylenetetrazole; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012977:Sodium Nitrite