Kinoshita K, Fujitsuka T, Yamamura M, Matsuoka Y
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Eur J Pharmacol. 1995 Feb 14;274(1-3):65-72. doi: 10.1016/0014-2999(94)00712-g.
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.
将新型促甲状腺激素释放激素（TRH：L-焦谷氨酰-L-组氨酰-L-脯氨酰胺）类似物TA-0910（1-甲基-(S)-4,5-二氢乳清酸-L-组氨酰-L-脯氨酰胺）对共济失调的影响与口服TRH的影响进行了比较。所使用的共济失调模型包括表现出小脑和纹状体基因功能障碍的滚动小鼠名古屋品系（RMN）、由3-乙酰吡啶（3-AP，40mg/kg，腹腔注射）诱导下橄榄化学性退变的大鼠以及由机械压迫诱导胸段脊髓损伤的大鼠。TA-0910（每天1、3、10mg/kg）对所有这些共济失调模型均明显显示出改善作用。TA-0910（每天10mg/kg）对RMN步态的剂量依赖性作用在其2周给药结束后持续至2周。TRH（每天100、300mg/kg）对RMN和3-AP处理的大鼠的共济失调也显示出改善作用。TA-0910对共济失调的改善作用比TRH强100 - 300倍。
