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

• Published in: Biological & pharmaceutical bulletin 1997/01/15, Vol.20(1), pp.36-39
• Main Authors: KINOSHITA, Kiyoshi, FUKUSHIMA, Takeshi, KODAMA, Yasuhiko, SUGIHARA, Juko, YAMAMURA, Michio, MATSUOKA, Yuzo
• Format: Article
• Language: English
• Subjects: Animals; Ataxia - drug therapy; Behavior, Animal - drug effects; Biological and medical sciences; chronic anti-ataxic effect; drug concentration; Male; Medical sciences; Mice; Mice, Mutant Strains; Miscellaneous; Neuropharmacology; Nootropic Agents - pharmacology; Pharmacology. Drug treatments; Rolling mouse Nagoya (RMN); TA-0910 (TRH analog); Thyrotropin-Releasing Hormone - administration & dosage; Thyrotropin-Releasing Hormone - analogs & derivatives; Thyrotropin-Releasing Hormone - pharmacokinetics; Thyrotropin-Releasing Hormone - pharmacology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.20.36

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.