Journal
NEUROREPORT
Volume 19, Issue 5, Pages 589-593Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0b013e3282f97b64
Keywords
agonist efficacy; methadone; opioid; potassium channel block
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Funding
- Medical Research Council [G0601841B, G0600943] Funding Source: researchfish
- Medical Research Council [G0600943] Funding Source: Medline
- MRC [G0600943] Funding Source: UKRI
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There is confusion in the literature concerning the relative agonist efficacy of methadone at mu-opioid receptors (MOPrs). Here, we confirm that methadone is a full agonist in guanosine 5'-O-[gamma-thio]triphosphate (GTP gamma S) 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 alpha(2)-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.
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