Effect of a noncompetitive antagonist (MK-801) of NMDA receptors on convulsions and brain amino acid level in E1 mice |
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Authors: | Keiko Sato Kiyoshi Morimoto Midori Akitane Mori Saburo Otsuki |
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Institution: | (1) Department of Neuropsychiatry Institute for Neurobiology, Okayama University Medical School, Okayama, Japan;(2) Department of Neurochemistry Institute for Neurobiology, Okayama University Medical School, Okayama, Japan;(3) Sanyoso Hospital, 685 Higashikiwa, 755-02 Ube, Japan |
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Abstract: | 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 induced 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 -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. |
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Keywords: | MK-801 NMDA receptors noncompetitive antagonist E1 mice epilepsy glycine |
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