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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.
AuthorsA I Faden, I Sacksen, L J Noble
JournalBrain research (Brain Res) Vol. 448 Issue 2 Pg. 287-93 (May 17 1988) ISSN: 0006-8993 [Print] Netherlands
PMID3132308 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • montirelin
  • Thyrotropin-Releasing Hormone
  • L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide
  • Pyrrolidonecarboxylic Acid
Topics
  • Animals
  • Evoked Potentials, Somatosensory
  • Molecular Conformation
  • Pyrrolidonecarboxylic Acid (analogs & derivatives)
  • Rats
  • Spinal Cord Injuries (drug therapy, pathology, physiopathology)
  • Thyrotropin-Releasing Hormone (analogs & derivatives, therapeutic use)
  • Time Factors

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