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Pharmacol Biochem Behav. 2008 Nov;91(1):115-20. doi: 10.1016/j.pbb.2008.06.019. Epub 2008 Jun 30.

The analgesic efficacy of fentanyl: relationship to tolerance and mu-opioid receptor regulation.

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1
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.

Abstract

This study determined if fentanyl analgesic efficacy predicts the magnitude of tolerance and mu-opioid receptor regulation. To estimate efficacy, mice were injected i.p. with saline or clocinnamox (CCAM), an irreversible mu-opioid receptor antagonist, (0.32-25.6 mg/kg) and 24 h later fentanyl cumulative dose-response studies were conducted. CCAM dose dependently shifted the fentanyl dose-response function to the right. The apparent efficacy (tau) of fentanyl, based on the operational model of agonism, was estimated as 58, indicating that fentanyl is a high analgesic efficacy agonist. Next, mice were infused with fentanyl (1, 2 or 4 mg/kg/day) for 7 days. Controls were implanted with placebo pellets. At the end of 7 days, morphine cumulative dose-response studies or mu-opioid receptor saturation binding studies were conducted. Fentanyl infusions dose dependently decreased morphine potency with the highest fentanyl dose reducing morphine potency by approximately 6 fold. Chronic infusion with fentanyl (4 mg/kg/day) significantly reduced mu-opioid receptor density by 28% without altering affinity, whereas lower infusion doses had no effect. Taken together, the present results strengthen the proposal that opioid analgesic efficacy predicts mu-opioid receptor regulation and the magnitude of tolerance.

PMID:
18640146
PMCID:
PMC2597555
DOI:
10.1016/j.pbb.2008.06.019
[Indexed for MEDLINE]
Free PMC Article
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