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 γ-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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Sherwin, A., Robitaille, Y., Quesney, F., Olivier, A., Villemure, J., Leblanc, R., Feindel, W., Andermann, E., Gotman, J., Andermann, F., Ethier, R., and Kish, S. 1988. Excitatory amino acids are elevated in human epileptic cerebral cortex. Neurology 38:920–923.
Janjua, N. A., Metrakos, J. D., and van Gelder, N. M. 1982. Plasma amino acids in epilepsy. Pages 181–197,in V. E., Anderson, W. A. Hauser, J. K. Penry and C. F. Sing (eds.), Genetic Basis of the Epilepsies, Raven Press, New York.
Watkins, J. C., and evans, R. H. 1981. Excitatory amino acid transmitters. Am. Rev. Pharmacol. Toxicol. 21:165–204.
Herron, C. E., Lester, R. A. J., Coan, E. J., and Collingridge, G. L. 1986. Frequency-depencent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism. Nature (Lond.) 322:265–267.
Morimoto, K., Holmes, K. H., and Goddard, G. V. 1987. Kindling induced changes in EEG recorded during stimulation from the site of stimulation: III. Direct pharmacological manipulations of the kindled amygdala. Exp. Neurol. 97:17–34.
Piredda, S., and Gale, K. 1986. Role of excitatory amino acid transmission in the genesis of seizures elicited from the deep prepiriform cortex. Brain Res. 377:205–210.
Clineschmidt, B. V., Martin, G. E., and Bunting, P. R. 1982. Anticonvulsant activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cycloheptene-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympahtomimetic, and apparent anxiolytic properties. Drug Devel. Res. 2:123–134.
Sato, K., Morimoto, K. and Okamoto, M. 1988. Anticonvulsant action of noncompetitive antagonist of NMDA receptors (MK-801) in the kindling model of epilepsy. Brain Res. 463:12–20.
Imaizumi, K., Ito, S., Kutsukake, G., Takizawa, T., Fujiwara, K. and Titikawa, K. Epilepsy like anomaly of mice. Jikken Dobutsu (Bulletin of the Experimental Animals, Tokyo) 8:6–10.
Mori, A. 1988. E1 mice: Neurochemical approach to the seizure mechanism. Neurosciences 14:275–285.
Suzuki, J. and Nakamoto, Y. 1977. Seizure patterns and electroencephalograms of E1 mouse. Electroencephalogr. Clin. Neurophysiol. 43:299–311.
Glowinsky, J. and Iversen, L. L. 1966. Regional studies of catecholamines in the rat brain. I. disposition of [3H]norepinephrine, [3H]dopamine and [3H]DOPA in various regions of the brain. J. Neurochem. 13:655–669.
Shimada, M., Kabuto, H. and Yokoi, I. 1987. The effect of α-phosphono ω-aminocarboxylic acids, on seizures and brain amino acid levels in E1 mice. Research Communications in Chemical Pathology and Pharmacology 57:359–373.
Chapman, A. G., Meldrum, B. S., Nanji, N. and Watkins, C. 1987. Anticonvulsant action and biochemical effects in DBA/2 mice of CPP (3-((±)2-carboxypinerazin-4-yl)-propyl-1-phosphonate), and novel N-methyl-d-aspartate antagonist. Eur. J. Pharmacol. 139:91–96.
Naruse, H., Kato, M., Kurokawa, M., Haba, R. and Yabe, T. 1960. Metabolic defects in a convulsive strain of mouse. J. Neurochem. 5:359–369.
Hiramatsu, M., Suzuki, S., Edamatsu, R., Shimada, M. and Mori, A. 1986. 20th Annual Meeting of the Japan Epilepsy Society.
Cotman, C. W., Monaghan, D. T., Ottersen, O. P. and Storm-Mathisen, J. 1987. Anatomical organization of Excitatory amino acid receptors and their pathways. Trends Neurosci. 10:273–280.
Ishida, N., Kasamo, K., Nakamoto, Y. and Suzuki, J. 1987. The roles of partial complex and hippocampus in seizures of the E1 mouse. Jap. J. Psychiatr. Neurol. 41:498–499.
Benavides, J., Rivy, J. P., Carter, C. and Scatton, B. 1988. Differential modulation of [3H]TCP binding to the NMDA receptor by L-glutamate and glycine. Eur. J. Pharmacol. 149:67–72.
Johnson, J. W. and Ascher, P. 1987. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531.
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Sato, K., Morimoto, K., Midori et al. Effect of a noncompetitive antagonist (MK-801) of NMDA receptors on convulsions and brain amino acid level in E1 mice. Neurochem Res 14, 741–744 (1989). https://doi.org/10.1007/BF00964951
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DOI: https://doi.org/10.1007/BF00964951