QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.121749v1 322/2/661    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hume, S. P. Articles by Nutt, D. J. Search for Related Content PubMed PubMed Citation Articles by Hume, S. P. Articles by Nutt, D. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB MORPHINE OXYCODONE QUININE Medline Plus Health Information Nuclear Scans

NEUROPHARMACOLOGY

Low Sensitivity of the Positron Emission Tomography Ligand [¹¹C]Diprenorphine to Agonist Opiates

Hammersmith Imanet Ltd., Hammersmith Hospital, London, United Kingdom (S.P.H., V.N., E.H., R.A.); Psychopharmacology Unit, University of Bristol, Bristol, United Kingdom (A.R.L.-H., D.J.N.); and Department of Palliative Medicine, Bristol Haematology and Oncology Centre, Bristol, United Kingdom (A.N.D.)

Previously, we reported minimal opioid receptor occupancy following a clinical dose of the µ-opioid agonist, methadone, measured in vivo using positron emission tomography (PET) with [¹¹C]diprenorphine and subsequently used rats to obtain experimental data in support of a high receptor reserve hypothesis (Melichar et al., 2005). Here, we report on further preclinical studies investigating opioid receptor occupancy with oxycodone (µ- and -receptor agonist), morphine (µ-receptor agonist), and buprenorphine (partial agonist at the µ-receptor and antagonist at the - and -receptors), each given at antinociceptive doses. In vivo binding of [¹¹C]diprenorphine was not significantly reduced after treatment with the full agonists but was reduced by 90% by buprenorphine. In addition, given that [¹¹C]diprenorphine is a non-subtype-specific PET tracer, there was no regional variation that might feasibly be interpreted as due to differences in opioid subtype distribution. The data support minimal competition between the high-efficacy agonists and the non-subtype-selective antagonist radioligand and highlight the limitations of [¹¹C]diprenorphine PET to monitor in vivo occupancy. Alternative means may be needed to address clinical issues regarding opioid receptor occupancy that are required to optimize treatment strategies.

Address correspondence to: David J. Nutt, Psychopharmacology Unit, Dorothy Hodgkin Building, Whitson Street, University of Bristol, Bristol, BS1 3NY, UK. E-mail: david.j.nutt{at}bristol.ac.uk

This article has been cited by other articles:

				H. Boecker, T. Sprenger, M. E. Spilker, G. Henriksen, M. Koppenhoefer, K. J. Wagner, M. Valet, A. Berthele, and T. R. Tolle The Runner's High: Opioidergic Mechanisms in the Human Brain Cereb Cortex, November 1, 2008; 18(11): 2523 - 2531. [Abstract] [Full Text] [PDF]

				G. Henriksen and F. Willoch Imaging of opioid receptors in the central nervous system Brain, May 1, 2008; 131(5): 1171 - 1196. [Abstract] [Full Text] [PDF]