GTS-21, a Nicotinic Agonist, Attenuates Multiple Infarctions and Cognitive Deficit Caused by Permanent Occlusion of Bilateral Common Carotid Arteries in Rats

元データ 1998-12-01 社団法人 日本薬理学会

概要

We examined the effects of GTS-21 [3-(2, 4-dimethoxybenzylidene)-anabaseine dihydrochloride], a nicotinic agonist, on histopathological changes of the brain and radial maze learning performance in rats with permanent occlusion of the bilateral common carotid arteries (2VO) and elucidated whether this compound has a protective effect against the neuronal degeneration and spatial cognitive deficit caused by chronic ischemia. Rats were administered GTS-21 (1 and 10 mg/kg, p.o.) or vehicle 24 hr and 30 min before the 2VO operation and then once daily for 2 months after the operation. The 2VO rats given vehicle had multiple infarctions in the cerebral cortex, hippocampus and striatum and rarefaction in the white matter at 2 months after the operation, although the number and distribution of infarctions varied among individual animals. In addition, the 2VO rats given vehicle showed a higher rate of errors in the acquisition trials of the 8-arm radial maze task than sham-operated controls. However, 2VO rats treated with GTS-21 (1 and 10 mg/kg, p.o.) showed significantly decreased neuropathological changes and less errors in the acquisition trials compared to the vehicle-treated 2VO rats. These results indicate that GTS-21 attenuates impairment of spatial cognitive deficit and progressive neuronal degeneration induced by 2VO and suggest that this compound is beneficial for the treatment of neurodegenerative diseases following chronic cerebral hypoperfusion.

著者

南里 真人 大鵬薬品工業株式会社 薬理研究所
渡辺 裕司 International Research Center For Traditional Medicine Toyama Prefecture International Health Comple
Watanabe Hiroshi Department of Cardiology, Niigata City General Hospital
MURAKAMI Yukihisa Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical Univers
MATSUMOTO Kinzo Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical Univers
Murakami Yukihisa 富山大学和漢医薬学総合研究所 複合薬物薬理学
Mukarami Yukihisa Institute Of Natural Medicine Toyama Medical And Pharmaceutical University
Murakami Yukihisa Division Of Medicinal Pharmacology Institute Of Natural Medicine Toyama Medical And Pharmaceutical U
Murakami Yukihisa Research Institute For Wakan-yaku (traditional Sino-japanese Medicines)
Murakami Yukihisa Department Of Pharmacology Institute Of Natural Medicine:21st Century Coe Program Toyama Medical And
Murakami Yuko Department Of Bioactive Molecules National Institute Of Infectious Diseases
Matsumoto Kinzo Div. Of Medicinal Pharmacology Inst. Of Natural Medicine Univ. Of Toyama
Matsumoto Kinzo Department Of Pharmacology Institute Of Natural Medicine:21st Century Coe Program Toyama Medical And
南里 真人 Department Of Pharmacology Taiho Pharmaceutical Co. Ltd.
NANRI Masato Section of Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd.
MIYAKE Hidekazu Section of Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd.
Miyake Hidekazu Department Of Pharmacology Taiho Pharmaceutical Co. Ltd.
Miyake Hidekazu Cardiovascular Science Research Laboratory Hanno Research Center Taiho Pharmaceutical Co. Ltd.
Matsumoto Kinzo 富山大学和漢医薬学総合研究所 複合薬物薬理学
Murakami Y Department Of Bioactive Molecules National Institute Of Infectious Diseases
Murakami Y Toho Univ. Chiba Jpn
Watanabe Hiroshi Department Of Applied Chemistry And Bioengineering Graduate School Of Engineering Osaka City Univers

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