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

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

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Department of Physiology and Pharmacology, University of Bristol, Bristol, UK.


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.

[Indexed for MEDLINE]

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