Studies of the roles of NMDA and AMPA glutamate receptors in the mechanism of corasole convulsions in mice.
Experiments on mice were performed to study the ability of monocationic and dicationic adamantane and phenylcyclohexyl derivatives to prevent convulsive syndrome induced by i.p. corasole (pentylenetetrazole; 80 mg/kg). Monocationic phenylcyclohexyl derivatives, which are selective blockers of NMDA glutamate receptor channels, along with memantine and MK-801, effectively prevented the appearance of the clonic and tonic components of convulsions at micromolar concentrations. Their dicationic analogs, which block both NMDA and AMPA receptor channels, were ineffective against clonic convulsions, but prevented corasole-induced tonic convulsions at much lower concentrations. The convulsive action of corasole, whose primary target is weakening of the inhibitory action of GABA, appears to be mediated by glutamatergic synaptic transmission. NMDA receptors have a much greater involvement than AMPA receptors in the genesis of clonic convulsions, while AMPA receptor activation appears to be an important component of tonic convulsions.
Lukomskaya
N Ya
NY
I. M. Sechenov Institute of Evolutionary Physiology and Biology, Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia.
Rukoyatkina
N I
NI
Gorbunova
L V
LV
Gmiro
V E
VE
Magazanik
L G
LG
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000737:chemistry; 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 / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D010433:Pentylenetetrazole