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

M. J. Christie, C. W. Vaughan, Susan Ingram

Research output: Contribution to journalArticle

48 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalInflammation Research
Volume48
Issue number1
DOIs
StatePublished - 1999

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Lipoxygenase Inhibitors
Arachidonic Acid
Metabolism
Opioid Analgesics
Brain
Non-Steroidal Anti-Inflammatory Agents
Neurons
Arachidonate 12-Lipoxygenase
Arachidonate 5-Lipoxygenase
Cyclooxygenase 1
Narcotic Antagonists
Neurology
Opioid Receptors
Prostaglandin-Endoperoxide Synthases
Metabolites
Mesencephalon
Prostaglandins
Neurotransmitter Agents
Analgesics
Central Nervous System

Keywords

  • 5-Lipoxygenase
  • Arachidonic acid
  • NSAID
  • Opioid
  • Pain

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)
  • Immunology
  • Cell Biology

Cite this

Opioids, NSAIDS and 5-lipoxygenase inhibitors act synergistically in brain via arachidonic acid metabolism. / Christie, M. J.; Vaughan, C. W.; Ingram, Susan.

In: Inflammation Research, Vol. 48, No. 1, 1999, p. 1-4.

Research output: Contribution to journalArticle

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