Anticonvulsant effects of antagonists of the N-methyl-D-aspartate receptor complex in a genetic model of epilepsy: the quaking mouse.
Tonic-clonic convulsions of mutant quaking mice were antagonized by the intracerebroventricular injection of N-methyl-D-aspartate receptor antagonists. The competitive antagonists, CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)-2-piperidine carboxylic acid), exerted a partial anticonvulsant action, with ED50S of 0.115 and 0.076 nmol, respectively. The non-competitive antagonists, TCP (1-(1-(2-thienyl)cyclohexyl)piperidine) and MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine), provided full protection, with ED50s of 4.49 and 2.67 nmol, respectively. The competitive antagonists elicited a marked ataxia whereas the non-competitive antagonists did not have side-effects. These results might reflect the involvement of glutamatergic neurotransmission in the convulsions of the quaking mutants.
Mitrovic
N
N
Laboratoire Neurochimie-Anatomie, Institut des Neurosciences, CNRS-UPMC, Paris, France.
Besson
M J
MJ
Maurin
Y
Y
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008821:Mice, Quaking; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D010812:Physical Stimulation; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; C012058:tenocyclidine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D010622:Phencyclidine