新規抗てんかん薬ゾニサミドの開発研究
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概要
- 論文の詳細を見る
Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimaize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.
- 公益社団法人日本薬学会の論文
- 1996-07-25
著者
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伊藤 継孝
大日本製薬株式会社 研究管理部
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宇野 準
大日本製薬株式会社総合研究所
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宇野 準
大日本製薬株式会社
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黒川 美貴雄
大日本製薬株式会社総合研究所
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宇野 準
大日本製薬
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宇野 準
Research Laboratory Dainippon Pharmaceutical Co. Ltd.
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黒川 美貴雄
大日本製薬株式会社創薬研究所
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伊藤 継孝
大日本製薬(株)総合研究所
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清水 當尚
大日本製薬株式会社
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清水 當尚
大日本製薬株式会社創薬研究所
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