NT69L, a novel analgesic, shows synergy with morphine

M. Boules, A. Shaw, Y. Liang, D. Barbut, E. Richelson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background: Neurotensin (NT) is a neuropeptide with antinociceptive effects that are mediated through NT receptors, of which there are three known subtypes (NTS1, NTS2, and NTS3). Morphine is a μ-opioid receptor agonist commonly used for pain treatment but is associated with side effects that can be serious. We hypothesize that selective NT receptor agonists may represent a novel class of analgesics and their use in conjunction with morphine will have synergistic properties which may reduce the dose of morphine administered and its side effects. Methods: The antinociceptive activity of an NT agonist (NT69L) and morphine was studied in rats using the hot plate test to determine if there is synergism between the two drugs in reducing pain. The NTS2 receptor antagonist, levocabastine, was used to determine the receptor subtype involved in the analgesic effect of NT69L and morphine. Results: The administration of both NT69L and morphine resulted in a dose-dependent analgesic effect. The isobolographic analysis demonstrated that the combination of sub-analgesic doses of NT69L and morphine was synergistic in the hot plate test. Pretreatment with the NTS2 receptor antagonist, levocabastine attenuated the antinociceptive effect of NT69L and the combined effect of NT69L and morphine in the hot plate test. Conclusion: The results support the hypothesis that the synergistic combination of NT69L and morphine would improve the pharmacological treatment of pain while minimizing specific adverse effects of each of the drugs at a higher dose. NTS2 is important for the antinociceptive effect of NT69L and morphine.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalBrain Research
Volume1294
DOIs
StatePublished - Oct 6 2009

Keywords

  • Antinociception
  • Hot plate
  • Morphine
  • Neurotensin
  • Rat
  • Synergism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Boules, M., Shaw, A., Liang, Y., Barbut, D., & Richelson, E. (2009). NT69L, a novel analgesic, shows synergy with morphine. Brain Research, 1294, 22-28. https://doi.org/10.1016/j.brainres.2009.07.086