Akinori Akaike (1), Takehiko Maeda (1), Satoshi Kaneko (1,#) and Yutaka
Tamura (2)
(1) Department of Pharmacology, Graduate School of Pharmaceutical Sciences,
Kyoto University, Kyoto 606-01, Japan
(2) Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences,
Fukuyama University, Fukuyama 729-02, Japan
(#) Present address: Yokohama Research Center, Mitsubishi Chemical Corporation,
Yokohama 277, Japan
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.
Keywords: Cerebral cortex, Glutamate, MKC-231