Methadone

Does it really have low efficacy at mu-opioid receptors?

I Rodriguez-Martin, E Braksator, C P Bailey, S Goodchild, N V Marrion, E Kelly, G Henderson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)589-593
Number of pages5
JournalNeuroreport
Volume19
Issue number5
DOIs
Publication statusPublished - Mar 2008

Fingerprint

mu Opioid Receptor
Methadone
Guanosine 5'-O-(3-Thiotriphosphate)
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Calcium-Activated Potassium Channels
Guanosine
GTP-Binding Proteins
Adrenergic Receptors

Cite this

Rodriguez-Martin, I., Braksator, E., Bailey, C. P., Goodchild, S., Marrion, N. V., Kelly, E., & Henderson, G. (2008). Methadone: Does it really have low efficacy at mu-opioid receptors? Neuroreport, 19(5), 589-593. https://doi.org/10.1097/WNR.0b013e3282f97b64

Methadone : Does it really have low efficacy at mu-opioid receptors? / Rodriguez-Martin, I; Braksator, E; Bailey, C P; Goodchild, S; Marrion, N V; Kelly, E; Henderson, G.

In: Neuroreport, Vol. 19, No. 5, 03.2008, p. 589-593.

Research output: Contribution to journalArticle

Rodriguez-Martin, I, Braksator, E, Bailey, CP, Goodchild, S, Marrion, NV, Kelly, E & Henderson, G 2008, 'Methadone: Does it really have low efficacy at mu-opioid receptors?', Neuroreport, vol. 19, no. 5, pp. 589-593. https://doi.org/10.1097/WNR.0b013e3282f97b64
Rodriguez-Martin I, Braksator E, Bailey CP, Goodchild S, Marrion NV, Kelly E et al. Methadone: Does it really have low efficacy at mu-opioid receptors? Neuroreport. 2008 Mar;19(5):589-593. https://doi.org/10.1097/WNR.0b013e3282f97b64
Rodriguez-Martin, I ; Braksator, E ; Bailey, C P ; Goodchild, S ; Marrion, N V ; Kelly, E ; Henderson, G. / Methadone : Does it really have low efficacy at mu-opioid receptors?. In: Neuroreport. 2008 ; Vol. 19, No. 5. pp. 589-593.
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