EFFECTS OF TA-0910, A NOVEL ORALLY-ACTIVE THYROTROPIN-RELEASING-HORMONE ANALOG, ON THE GAIT OF ATAXIC ANIMALS

The effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolinamide), a new thyrotropin-releasing hormone (TRH: L-pyroglutamyl-L-histidyl-L-prolinamide) analog, on ataxia were compared with those of TRH given by oral administration. The ataxic models used were the Rolling mouse Nagoya (RMN) showing genetic dysfunction of the cerebellum and striatum, rats with chemical degeneration of the inferior olive induced by 3-acetylpyridine (3-AP, 40 mg/kg, i.p.) and rats with a lesion of the thoracic spinal cord induced by mechanical compression. TA-0910 (1, 3, 10 mg/kg per day) clearly showed ameliorating effects on all these ataxic models. The dose-dependent effect of TA-0910 (10 mg/kg per day) on the gait of RMN was sustained until 2 weeks after the end of its 2-week administration. TRH (100, 300 mg/kg per day) also showed ameliorating effects on ataxia in RMN and 3-AP-treated rats. The ameliorating action of TA-0910 on ataxia was 100-300 times more potent than that of TRH.