Low Sensitivity of the Positron Emission Tomography Ligand [11c]diprenorphine to Agonist Opiates.
From: Hammersmith Imanet Ltd., Hammersmith Hospital, London, United Kingdom.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Aug 2007
- ISSN: 0022-3565
- Volume: 322
- Issue: 2
- Pages: 661-7
- Medium: Print
- Language: English
- Citation (JAMA): Hume Susan P, Lingford-Hughes Anne R, Nataf Valerie, et al. Low Sensitivity of the Positron Emission Tomography Ligand [11c]diprenorphine to Agonist Opiates.. J. Pharmacol. Exp. Ther. Aug 2007;322:661-7
Abstract
Previously, we reported minimal opioid receptor occupancy following a clinical dose of the micro-opioid agonist, methadone, measured in vivo using positron emission tomography (PET) with [(11)C]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 (micro- and kappa-receptor agonist), morphine (micro-receptor agonist), and buprenorphine (partial agonist at the micro-receptor and antagonist at the delta- and kappa-receptors), each given at antinociceptive doses. In vivo binding of [(11)C]diprenorphine was not significantly reduced after treatment with the full agonists but was reduced by approximately 90% by buprenorphine. In addition, given that [(11)C]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 [(11)C]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.
Mesh Headings (Keywords): Analgesics, Opioid, Animals, Brain, Brain Stem, Buprenorphine, Carbon Radioisotopes, Cerebellum, Competitive Bidding, Diprenorphine, Limbic System, Male, Morphine, Oxycodone, Positron-Emission Tomography, Prosencephalon, Quinine, Rats, Rats, Sprague-Dawley, Receptors, Opioid, Reproducibility of Results, Tissue Distribution
Check for Full Text / PubMed Unique Identifier (PMID): 17488881
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