Effect of a noncompetitive antagonist (MK-801) of NMDA receptors on convulsions and brain amino acid level in E1 mice.
Anticonvulsant action of MK-801, a novel noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor, was examined in genetically epileptic E1 mice. Systemic injection of MK-801 (0.1-1.0 mg/kg) potently suppressed generalized tonic-clonic convulsions of in a dose-dependent manner (ED50, 0.17 mg/kg). This anticonvulsant effect of MK-801 appeared at a dose which did not induce any obvious behavioral changes. Following the administration of a fully anticonvulsant dose of MK-801 (1 mg/kg), amino acid analysis revealed a significantly elevated level of glycine in the hippocampus. Levels of other amino acids including glutamate, aspartate, taurine, glutamine, alanine, and gamma-aminobutyrate were not changed either in the hippocampus or in the cerebral cortex. This study suggests that NMDA system may play an essential role in seizure-triggering mechanisms in E1 mouse.
Sato
K
K
Department of Neuropsychiatry, Okayama University Medical School.
Morimoto
K
K
Hiramatsu
M
M
Mori
A
A
Otsuki
S
S
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004827:Epilepsy / Q000188:drug therapy*; D006624:Hippocampus / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter
D000596:Amino Acids; D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate