Effects of T-82, a New Quinoline Derivative, on Cholinesterase Activity and Extracellular Acetylcholine Conventration in Rat Brain
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概要
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The effects of T-82 (2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate), a new quinoline derivative, on acetylcholinesterase (AChE) activity and acetylcholine (ACh) release were compared with those of the well-known cholinesterase inhibitors tacrine and E2020. T-82, tacrine and E2020 all concentration-dependently inhibited AChE in rat brain homogenate (IC50s = 109.4, 84.2 and 11.8 nM, respectively). In addition, although tacrine strongly inhibited butyrylcholinesterase (BuChE), T-82 and E2020 showed only weak activity on BuChE in human plasma. In ex vivo experiments, intraperitoneal administration of T-82 at a dose of 30 mg/kg inhibited AChE activity in the hippocampus, frontal cortex and parietal cortex of rats. The effect of T-82 on the extracellular ACh concentration in rat brain was measured using in vivo microdialysis. T-82 at doses of 10 and 30 mg/kg, i.p. increased the extracellular ACh concentration in the hippocampus and striatum in a dose-dependent manner. These findings suggest that T-82 activates the central cholinergic system by selectively inhibiting AChE activity, while weakly affecting peripheral BuChE activity, and that T-82 increases the extracellular ACh concentration in the brain, which is followed by inhibited AChE activity.
- 社団法人 日本薬理学会の論文
- 2002-02-01
著者
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KAMEI Junzo
Department of Pathophysiology, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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HASEGAWA Hiroshi
Centre for Research in Neurodegenerative Diseases Toronto University
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Ishikawa M
Central Research Laboratories Ssp Co. Ltd.
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Ishikawa Masago
Central Research Laboratories Ssp Co. Ltd.
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Ohta Megumi
Central Research Laboratories Ssp Co. Ltd.
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Kamei Junzo
Department Of Pathophysiology And Therapeutics Faculty Of Pharmaceutical Sciences Hoshi University
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Kamei Junzo
Department Of Pathophysilology & Therapeutics Faculty Of Pharmaceutical Sciences Hoshi Universit
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Ogawa Yoshihide
Central Research Laboratories Ssp Co. Ltd.
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ISOMAE Kazuo
Central Research Laboratories, SSP Co., Ltd.
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OGAWA Yoichiro
Central Research Laboratories, SSP Co., Ltd.
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KOHDA Tadayuki
Central Research Laboratories, SSP Co., Ltd.
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Isomae Kazuo
Central Research Laboratories Ssp Co. Ltd.
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Kohda Tadayuki
Central Research Laboratories Ssp Co. Ltd.
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Ogawa Yoichiro
Central Research Laboratories Ssp Co. Ltd.
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Hasegawa H
Central Research Laboratories Ssp Co. Ltd.
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Hasegawa Hiroshi
Central Research Laboratory Nippon Suisan Kaisha Ltd.
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