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
| Autor: | Yuzo Matsuoka, Takeshi Fukushima, Kiyoshi Kinoshita, Yasuhiko Kodama, Juko Sugihara, Michio Yamamura |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Ataxia Central nervous system Pharmaceutical Science Thyrotropin-releasing hormone Peptide hormone Drug withdrawal Mice Pharmacokinetics Oral administration Internal medicine medicine Animals Thyrotropin-Releasing Hormone Nootropic Agents Pharmacology Behavior Animal business.industry General Medicine medicine.disease Mice Mutant Strains Endocrinology medicine.anatomical_structure Hormone analog medicine.symptom business |
| Zdroj: | Biologicalpharmaceutical bulletin. 20(1) |
| ISSN: | 0918-6158 |
| Popis: | 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 24h 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 concentrations 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. |
| Databáze: | OpenAIRE |
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