Protective Effect of MKC-231, a Novel High Affinity Choline Uptake Enhancer, on Glutamate Cytotoxicity in Cultured Cortical Neurons.

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  • Akaike Akinori
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Maeda Takehiko
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Kaneko Satoshi
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University Present address: Yokohama Research Center, Mitsubishi Chemical Corporation
  • Tamura Yutaka
    Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

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  • Protective Effect of MKC-231 a Novel Hi

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Abstract

This study was performed to examine the neuroprotective action of 2-(2-oxopyrrolidin-1-yl)-N-(2, 3-dimethyl-5, 6, 7, 8-tetrahydrofuro[2, 3-b]quinolin-4-yl)acetoamide (MKC-231), which enhances choline uptake and acetylcholine release in the central nervous system. Glutamate neurotoxicity was assessed with cortical cultures obtained from fetal rats. Exposure of cultures to MKC-231 for 12 – 24 hr ameliorated glutamate cytotoxicity. MKC-231 reduced cytotoxicity induced by ionomycin, a calcium ionophore, but did not affect the cytotoxicity induced by S-nitrosocysteine, a nitric oxide (NO) donor. These findings suggest that MKC-231 protects against glutamate neurotoxicity by suppressing the NO formation triggered by Ca2+-influx.

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