Structure-activity relationships of TRH analogs in rat spinal cord injury

Abstract

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.