Chronic Anti-ataxic Actions of the Novel Thyrotropin-Releasing Hormone (TRH) Analog, TA-0910,during and after Repeated Administration in Rolling Mouse Nagoya : Behavioral and Pharmacokinetic Studies
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概要
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Anti-ataxic effects of TA-0910,a novel thyrotropin-releasing hormone analog, in mice of the ataxic mutant mouse strain Rolling mouse Nagoya (RMN) are sustained beyond its 2-week oral administration period (Kinoshita et al., Eur. J. Pharmacol., 274,65-72,1995). We examined the concentration of TA-0910 in the central nervous system (CNS) of RMN after repeated administration in an attempt to clarify the mechanism of the sustained effect of the drug. Repeated administration of TA-0910 (3 mg/kg/d, i.p.) for 2 weeks produced a long-lasting ameliorating effect on ataxia in RMN, and this effect was maintained until 3 weeks after drug withdrawal. The concentrations of TA-0910 in the cerebrum and brain stem 24 h after the final administration were twice the concentration observed 24 h after single administration. The cerebellum cencentration of TA-0910 was more than 4 times that observed 24 h after final administration. After repeated administrations, the drug concentrtions in the brain tissues gradually decreased, but the drug was still detectable in the cerebrum and brain stem 3 weeks after withdrawal. However, these concentrations of TA-0910 3 weeks after withdrawal were as low those observed 24 h after single administration when there were no anti-ataxic effects. These observations suggest that the long-lasting ameliorating effect on the ataxia during and after repeated administration of TA-0910 is not ascribable to the drug remaining in the CNS of RMN.
- 公益社団法人日本薬学会の論文
- 1997-01-15
著者
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Kodama Y
Tohoku Univ. Sendai Jpn
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Matsuoka Yuzo
Discovery Researchlaboratory Tanabe Seiyaku Co. Ltd.
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Kawashima K
Nagoya Inst. Of Technol. Nagoya Jpn
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Yamamura Michio
Tanabe R&d Service Co. Ltd.
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KINOSHITA Kiyoshi
Pharmacology Department, Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.
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SUGIHARA Juko
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd.,
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FUKUSHIMA Takeshi
Pharmaceutical Development Research Laboratory Tanabe Seiyaku Co., Ltd.,
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KODAMA Yasuhiko
Pharmaceutical Development Research Laboratory Tanabe Seiyaku Co., Ltd.,
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YAMAMURA Michio
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,
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MATSUOKA Yuzo
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,
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Yamamura Michio
Pharmacology Department Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.
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Fukushima Takeshi
Pharmaceutical Development Research Laboratory Tanabe Seiyaku Co. Ltd.
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Kinoshita Kiyoshi
Pharmacology Department Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.
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SUGIHARA Juko
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co. Ltd.
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Sugihara Juko
Pharmaceutical Development Research Laboratory Tanabe Seiyaku Co., Ltd.,
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