Using [C-11]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: Clinical and preclinical studies

Melichar, Jan K., Hume, Susan P., Williams, Tim M., Daglish, Mark R. C., Taylor, Lindsay G., Ahmad, Rabia, Malizia, Andrea L., Brooks, David J., Myles, Judith S., Lingford-Hughes, Anne and Nutt, David J. (2005) Using [C-11]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: Clinical and preclinical studies. Journal of Pharmacology And Experimental Therapeutics, 312 1: 309-315. doi:10.1124/jpet.104.072686

Author Melichar, Jan K.
Hume, Susan P.
Williams, Tim M.
Daglish, Mark R. C.
Taylor, Lindsay G.
Ahmad, Rabia
Malizia, Andrea L.
Brooks, David J.
Myles, Judith S.
Lingford-Hughes, Anne
Nutt, David J.
Title Using [C-11]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: Clinical and preclinical studies
Journal name Journal of Pharmacology And Experimental Therapeutics   Check publisher's open access policy
ISSN 0022-3565
Publication date 2005-01-01
Sub-type Article (original research)
DOI 10.1124/jpet.104.072686
Open Access Status
Volume 312
Issue 1
Start page 309
End page 315
Total pages 7
Place of publication Bethesda, M.D, U.S.A.
Publisher American Society for Pharmacology Experimental Therapeutics
Language eng
Subject 110319 Psychiatry (incl. Psychotherapy)
Abstract Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [C-11] diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone ( 18 - 90 mg daily) had an [C-11] diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [C-11] diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [C-11] diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [C-11] diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [C-11] diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.
Keyword Pharmacology & Pharmacy
Opiate Receptor
C-11 Diprenorphine
Interindividual Variability
Endogenous Opioids
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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