Faden A I, Sacksen I, Noble L J
Department of Neurology, University of California, San Francisco.
Brain Res. 1988 May 17;448(2):287-93. doi: 10.1016/0006-8993(88)91265-6.
Effects of thyrotropin-releasing hormone (TRH) analogs were compared in rats to evaluate the structure-activity relationships of such compounds in the treatment of traumatic spinal cord injury. CG3703, a TRH analog having a modified amino-terminus, significantly improved motor recovery and somatosensory-evoked responses after trauma; in contrast, RX77368, which has a modified carboxy-terminus, was without effect, even at doses up to 10 mg/kg. These findings confirm and extend findings in cats, using other TRH analogs in a different model of spinal trauma. Together, data from rat and cat studies are consistent with the hypothesis that the integrity of the C-terminal amino acid may be critical for the beneficial effects of treatment with TRH and TRH analogs in experimental spinal injury, and suggest that a variety of other TRH analogs having substitutions of the pyroglutamyl or histidyl moieties of the tripeptide may also prove to be effective in the treatment of such injury.
在大鼠中比较了促甲状腺激素释放激素（TRH）类似物的作用，以评估此类化合物在治疗创伤性脊髓损伤中的构效关系。CG3703是一种具有修饰氨基末端的TRH类似物，可显著改善创伤后的运动恢复和体感诱发电位；相比之下，具有修饰羧基末端的RX77368即使在高达10 mg/kg的剂量下也没有效果。这些发现证实并扩展了在猫中使用其他TRH类似物在不同脊髓创伤模型中的研究结果。大鼠和猫的研究数据共同表明，C末端氨基酸的完整性对于TRH和TRH类似物在实验性脊髓损伤治疗中的有益作用可能至关重要，并表明多种其他具有三肽焦谷氨酰基或组氨酰基取代的TRH类似物也可能被证明对治疗此类损伤有效。
