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Related Experiment Videos

Dextromethorphan differentially affects opioid antinociception in rats.

Shiou-Lan Chen1, Eagle Yi-Kung Huang, Lok-Hi Chow

  • 1Graduate Institute of Medical Science, National Defense Medical Center, 161 Minchuan East Road, Sec. 6 Taipei, Taiwan, Republic of China.

British Journal of Pharmacology
|January 19, 2005
PubMed
Summary

Dextromethorphan (DM) enhances morphine

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Opioid analgesics like morphine are vital for pain relief but have side effects.
  • N-methyl-D-aspartate (NMDA) receptors are implicated in opioid analgesia, tolerance, and dependence.
  • Dextromethorphan (DM), an NMDA antagonist, may offer benefits when combined with opioids.

Purpose of the Study:

  • To investigate the impact of dextromethorphan (DM) on the antinociceptive effects of various opioids.
  • To explore potential pharmacokinetic mechanisms underlying these interactions.
  • To assess DM's effects on mu-opioid and kappa-opioid agonists.

Main Methods:

  • Utilized the tail-flick test in male Sprague-Dawley rats to evaluate antinociception.
  • Administered mu-opioid agonists (morphine, meperidine, codeine) and kappa-opioid agonists (nalbuphine, U-50,488H) with and without DM.

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  • Analyzed serum concentrations of morphine and codeine using High-Performance Liquid Chromatography (HPLC) to examine pharmacokinetic interactions.

    • Main Results:

    • Dextromethorphan (DM) potentiated the antinociceptive effects of morphine and meperidine but not codeine or kappa-opioid agonists.
    • DM increased acute serum morphine concentrations when coadministered with morphine.
    • DM attenuated codeine's antinociceptive effect and decreased its active metabolite (morphine) serum concentration.

    Conclusions:

    • Dextromethorphan (DM) differentially affects the antinociceptive properties of various opioids.
    • Pharmacokinetic interactions between DM and opioids, particularly concerning serum concentrations, partially explain these observed effects.
    • These findings suggest potential therapeutic strategies for optimizing opioid-based pain management by combining them with NMDA antagonists like DM.