Beneficial Effects of FKS-508 (AF102B), a Selective M<SUB>1</SUB> Agonist, on the Impaired Working Memory in AF64A-Treated Rats
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概要
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The effects of FKS-508 [AF102B; cis 2-methylspiro(1, 3-oxathiolane5, 3)quinuclidine], a selective M<SUB>1</SUB> muscarinic receptor agonist, were examined to predict the possible activity on memory disorders using a T-maze and radial-arm maze task in experimental amnesia models. The amnesia models were produced by bilateral intracerebroventricular injection of ethylcholine aziridinium ion (AF64A), a selective cholinotoxin, in rats. Repeated administrations of FKS-508 (5 mg/kg/day, i.p.) for 5 weeks significantly ameliorated impaired performance of AF64A-treated rats (AF64A-rats) in a delayed alternation task in the T-maze. Repeated administrations of FKS-508 (1 and 5 mg/kg/day, p.o.) for 5 weeks significantly ameliorated acquisition failures of AF64A.-rats in a radial-arm maze task. Single administration of FKS-508 (1 and 5 mg/kg, p.o.) significantly reduced the incorrect choices of AF64A-rats in a radial-arm maze task with 6 hr-delay time. No abnormalities in general behaviors, such as loss of appetite and ataxia, were observed in rats treated with FKS-508 repeatedly during 5 weeks. Our present results showed that FKS508 can ameliorate memory impairments in AF64A-rats with central cholinergic hypofunction without causing any behavioral abnormalities. FKS-508 may be considered as a candidate for the clinical examination of the cholinergic hypothesis of senile dementia of the Alzheimer type.
著者
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KAWANISHI Gosei
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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Kawanishi Gosei
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Iga Yoshinori
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Saito Yasunari
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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NAKAHARA Noboru
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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MIZOBE Fumio
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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MIZOBE Fumio
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd
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