Advertisement

Inflammation Research

, Volume 48, Issue 1, pp 1–4 | Cite as

Opioids, NSAIDs and 5-lipoxygenase inhibitors act synergistically in brain via arachidonic acid metabolism

  • M. J. Christie
  • C. W. Vaughan
  • S. L. Ingram

Abstract.

We have established that μ-opioid receptor activation causes a presynaptic inhibition of neurotransmitter release that is mediated by 12-lipoxygenase metabolites of arachidonic acid in midbrain neurons [1]. We further demonstrated that the efficacy of opioids was enhanced synergistically by treatment of brain neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism; cyclooxygenase (COX-1) and 5-lipoxygenase. These findings explain a mechanism of analgesic action of NSAIDs in the central nervous system that is both independent of prostanoid release and inhibited by opioid antagonists, as well as the synergistic interaction of opioids with NSAIDs. These findings also suggest new avenues for development of centrally active medications involving combinations of lowered doses of opioids and specific 5-lipoxygenase inhibitors.

Key words: Opioid — NSAID — 5-Lipoxygenase — Arachidonic acid — Pain 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Birkhäuser Verlag, Basel, 1999

Authors and Affiliations

  • M. J. Christie
    • 1
  • C. W. Vaughan
    • 1
  • S. L. Ingram
    • 1
  1. 1.Department of Pharmacology D06 and The Medical Foundation, The University of Sydney, NSW 2006, Australia, Fax +61 2 9351 3868, e-mail: macc@pharmacol.usyd.edu.auAU

Personalised recommendations