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Published on: July 29, 2014

(S)-(+)-methadone is more immunosuppressive than the potent analgesic (R)-(--)-methadone

Mark R Hutchinson1, Andrew A Somogyi

  • 1Department of Clinical and Experimental Pharmacology, University of Adelaide, Level 5, Medical School North, Frome Road, 5005, Adelaide, Australia. mark.hutchinson@adelaide.edu.au

International Immunopharmacology
|September 8, 2004
PubMed

Insights

This study reveals that while (R)-methadone provides pain relief, both (R)- and (S)-methadone enantiomers suppress immune cell proliferation in vivo, suggesting nonclassical opioid receptor involvement.

Area of Science:

  • Pharmacology
  • Immunology
  • Neuroscience

Background:

  • Methadone, a synthetic opioid, is administered as a racemic mixture.
  • Only the (R)-(--)-methadone enantiomer exhibits mu opioid receptor agonist activity.
  • In vitro studies suggest methadone affects immune function via nonclassical opioid receptors.

Purpose of the Study:

  • To investigate the stereoselectivity of methadone's analgesic and immunomodulatory effects in vivo.
  • To compare the in vivo effects of (R)-(--)-methadone, (S)-(+)-methadone, and racemic methadone on analgesia and splenocyte proliferation.

Main Methods:

  • Assessment of analgesia using the hot plate test in Balb/c mice.
  • Ex vivo evaluation of splenocyte proliferation following in vivo administration of methadone enantiomers.
  • Statistical analysis to determine the significance of observed effects compared to saline controls.

Main Results:

  • Significant analgesia was observed with racemic and (R)-(--)-methadone, but not with (S)-(+)-methadone.
  • Both (R)-(--)- and racemic methadone significantly inhibited basal splenocyte proliferation in vivo.
  • Unexpectedly, (S)-(+)-methadone induced a greater inhibition of splenocyte proliferation than (R)-(--)- and racemic methadone.

Conclusions:

  • Methadone's immune suppression in vivo is not solely mediated by classical opioid receptors.
  • Nonclassical opioid receptors, potentially at the central level, are implicated in methadone's immunomodulatory effects.
  • The observed immune suppression occurs at clinically achievable methadone doses.

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