[Role of NMDA and AMPA glutamate receptors in the mechanism of korazol-induced convulsions in mice].
The potency of mono- and dikationic derivatives of adamantane and phenylcyclohexyl to prevent seizures induced in mice by intraperitoneal administration of 80 mg/kg pentylenetetrazol (corazol), was studied. Monocationic derivatives of phenylcyclohexyl, being the selective channel blockers of NMDA glutamate receptors, as well memantine and MK-801 in micromolar concentrations, prevented both clonic and tonic components of corazol-induced convulsions. Their dicatonic derivatives which are channel blockers of NMDA and AMPA types of glutamate receptors, failed to prevent clonic seizures but at submicromolar concentrations prevented the tonic extensions provoked by corazol. Evidently, convulsive action of corazol originating from suppression of GABA-ergic inhibition is realized through activation of glutamergic synaptic transmission, and NMDA receptors are mainly involved in genesis of clonic seizures whereas activation of AMPA receptors is important for the tonic component of the corazol-induced syndrome.
Lukomskaia
N Ia
NIa
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Acad. Sci., 194223, St. Petersburg, pr. M. Toreza, 44, Russia.
Rukoiatkina
N I
NI
Gorbunova
L V
LV
Gmiro
V E
VE
Magazanik
L G
LG
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D010433:Pentylenetetrazole
Issledovanie roli NMDA i AMPA glutamatnykh retseptorov v mekhanizme korazolovykh sydorog u mysheĭ.