Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonist

Claire L. Neilan, Stephen M. Husbands, Simon Breeden, M. C. Ko, Mario D. Aceto, John W. Lewis, James H. Woods, John R. Traynor

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The development of buprenorphine as a treatment for opiate abuse and dependence has drawn attention to opioid ligands that have agonist actions followed by long-lasting antagonist actions. In a search for alternatives to buprenorphine, we discovered a bridged pyrrolidinomorphinan (BU72). In vitro, BU72 displayed high affinity and efficacy for mu-opioid receptors, but was also a partial delta-opioid receptor agonist and a full kappa-opioid receptor agonist. BU72 was a highly potent and long-lasting antinociceptive agent against both thermal and chemical nociception in the mouse and against thermal nociception in the monkey. These effects were prevented by mu-, but not kappa- or delta-, opioid receptor antagonists. Once the agonist effects of BU72 had subsided, the compound acted to attenuate the antinociceptive action of morphine. BU72 is too efficacious for human use but manipulation to reduce efficacy could provide a lead to the development of a treatment for opioid dependence.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalEuropean Journal of Pharmacology
Volume499
Issue number1-2
DOIs
StatePublished - Sep 19 2004
Externally publishedYes

Keywords

  • (Monkey)
  • (Mouse)
  • Agonism
  • Antagonism
  • Antinociception
  • mu-opioid receptor

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Characterization of the complex morphinan derivative BU72 as a high efficacy, long-lasting mu-opioid receptor agonist'. Together they form a unique fingerprint.

  • Cite this