Methadone: does it really have low efficacy at micro-opioid receptors?

Neuroreport. 2008 Mar 26;19(5):589-93. doi: 10.1097/WNR.0b013e3282f97b64.


There is confusion in the literature concerning the relative agonist efficacy of methadone at micro-opioid receptors (MOPrs). Here, we confirm that methadone is a full agonist in guanosine 5'-O-[gamma-thio]triphosphate (GTPgammaS) binding studies. Methadone, however, seems to have low efficacy in studies of MOPr activation of G-protein-gated potassium (GIRK) channels, but this is because it directly inhibits the GIRK channels. Methadone also inhibits alpha2-adrenoceptor-activated GIRK channels. Methadone is not a specific GIRK channel blocker. It also inhibits small conductance Ca2+-activated K+ (SK2) channels. We conclude that methadone is a full agonist at MOPrs that, as we and others have shown, induces MOPr desensitization and internalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Line, Transformed
  • Drug Interactions
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • In Vitro Techniques
  • Locus Coeruleus / cytology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Methadone / pharmacology*
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology*
  • Neurons / drug effects*
  • Neurons / physiology
  • Neurons / radiation effects
  • Protein Binding / drug effects
  • Rats
  • Receptors, Opioid, mu / drug effects*
  • Transfection


  • Narcotic Antagonists
  • Narcotics
  • Receptors, Opioid, mu
  • Naloxone
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Morphine
  • Methadone