Ameliorating effect of TA-0910. a novel TRH analog, on ataxia models

• Published in: Japanese Journal of Pharmacology 1992, Vol.58 (suppl.1), p.177-177
• Main Authors: Kinoshita, Kiyoshi, Pujitsuha, Tatsuya, Yamamura, Michio, Ishida, Ryuichi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)49030-6

We have reported that oral administration of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolineamide) for 22 consecutive days shows the ameliorating effect on 3-acetylpyridine-induced ataxia (79th. Regional Meeting (Kinki Area) of the Jpn. Pharm. Soc., 1991). Here, we studied the effects of oral administration of TA-0910 and TRH on genetic ataxia in Rolling Mouse Nagoya (RMN) and spinal cord injury-induced ataxia in the rat. TA-0910 ameliorated the ataxic movements in RMN at 3 mg/kg of single administration and at 1 mg/kg/day of consecutive administration for 14 days. In the latter experiment, the ameliorating effect vas observed even at the 2nd week after drug withdrawal. TRH (300 mg/kg/day for 14 days) also showed the ameliorating effect. TA-0910 (3 and 10 mg/kg/day for 42 days) promoted the recovery from the spinal cord injury-induced ataxia produced by compressing the cord at the 12th thoracic ventral level for 30 min with stainless steel screw (diameter： 2 mm, length： 5 mm). TRH (300 mg/kg/day for 42 days) showed no effect. These results suggest that TA-0910 have ameliorating effect not only on drug-induced ataxia, but also on genetic and traumatic ataxia. The ameliorating effects of TA-0910 on these ataxia models are discussed in connection with its central nervous system activation.