Methadone: does it really have low efficacy at μ-opioid receptors?
2008; Lippincott Williams & Wilkins; Volume: 19; Issue: 5 Linguagem: Inglês
10.1097/wnr.0b013e3282f97b64
ISSN1473-558X
AutoresIván Rodríguez-Martín, Ellen Braksator, Christopher Bailey, Sam Goodchild, Neil V. Marrion, Eamonn Kelly, Graeme Henderson,
Tópico(s)Neuropeptides and Animal Physiology
ResumoThere is confusion in the literature concerning the relative agonist efficacy of methadone at μ-opioid receptors (MOPrs). Here, we confirm that methadone is a full agonist in guanosine 5′-O-[gamma-thio]triphosphate (GTPγS) 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 α2-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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