title: [Comparison of the anticonvulsant activity of organic mono- and di-cations and their potential to inhibit NMDA and AMPA glutamate receptors].
abstract: Effects of mono- and dicationic derivatives of adamantine and phenylcyclohexyl were studied on: (i) open channels of NMDA and AMPA glutamate receptors in the experiments on the isolated rat brain neurones, and (ii) convulsions induced by intraventricular injections of NMDA or kainate in mice. Monocations inhibited the NMDA receptors in vitro and prevented convulsions induced by NMDA in vivo, but failed to affect both the AMPA receptors and kainite-induced convulsions. Dications (IEM-1754 and IEM-1925) revealed both anti-NMDA and anti-AMPA potency in vitro, were highly effective against kainite-induced convulsions and excelled monocations in preventing the NMDA-induced ones. Evidently some steps connected with the AMPA receptor activity are involved in the genesis of the NMDA-induced convulsions. Anticonvulsant potency of IEM-1754 and IEM-1925 is comparable with those of known NMDA receptor inhibitors: memantine and MK-801. The IEM-1754 and IEM-1925 show no side effects. An incomplete correspondence between the activity in vitro and in vivo found studying some derivatives, may be due to peculiarities of their pharmacokinetics.
authors.affiliation: I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Acad. Sci., 194223, St. Petersburg, pr. M. Toreza, 44, Russia.
authors.forename: N Ia
authors.initials: NIa
authors.lastname: Lukomskaia
authors.forename: N I
authors.initials: NI
authors.lastname: Rukoiatkina
authors.forename: L V
authors.initials: LV
authors.lastname: Gorbunova
authors.forename: V E
authors.initials: VE
authors.lastname: Gmiro
authors.forename: K V
authors.initials: KV
authors.lastname: Bol'shakov
authors.forename: L G
authors.initials: LG
authors.lastname: Magazanik
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002412:Cations; D003292:Convulsants; D003959:Diamines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D002412:Cations; D003292:Convulsants; D003959:Diamines; C092754:IEM 1754; C406748:IEM 1925; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000218:Adamantane