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Interaction of μ‐opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice
Author(s) -
Kögel Babette,
Christoph Thomas,
Straβburger Wolfgang,
Friderichs Elmar
Publication year - 2005
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2005.02.002
Subject(s) - buprenorphine , hydromorphone , pharmacology , opioid , analgesic , (+) naloxone , fentanyl , morphine , naltrexone , medicine , oxycodone , opioid receptor , opioid antagonist , partial agonist , oxymorphone , antagonist , anesthesia , receptor
Buprenorphine is a potent opioid analgesic with partial agonistic properties at μ‐opioid receptors. This study investigated the interaction potential with several full μ‐agonists in the tail‐flick test in mice. We further examined the reversibility of buprenorphine antinociception by different μ‐opioid receptor antagonists. Combination of buprenorphine with morphine, oxycodone, hydromorphone and fentanyl in the analgesic dose range resulted in additive or synergistic effects. When given after the decline of the acute buprenorphine effect, both morphine and fentanyl also showed full efficacy. A moderate antagonistic effect according to the partial μ‐agonistic properties of buprenorphine was only seen when high doses exceeding the therapeutic dose ranges were combined. Under these conditions antinociception of morphine was reduced to the effect of buprenorphine alone. Prophylactic administration of naloxone (10 mg/kg i.v.), naltrexone (1 mg/kg i.v.) and clocinnamox (5 mg/kg s.c.) fully and persistently blocked the antinociception of a high dose of buprenorphine. An established effect of buprenorphine was less sensitive, although repeated administration of naloxone induced complete antagonism, as did the irreversible antagonist clocinnamox under prophylactic and curative treatment conditions. Our results suggest that the antinociceptive effect of buprenorphine is mainly, if not exclusively, mediated by activation of μ‐opioid receptors. They confirm clinical experience that in the analgesic dose range a switch between buprenorphine and full μ‐agonists is possible without loss of analgesic efficacy and without a refractory period between the termination of buprenorphine analgesia and the onset of action of the new μ‐opioid treatment. Antinociception of buprenorphine is sensitive towards μ‐opioid receptor antagonists and incomplete inhibition can be improved by increasing the dose or repetitive dosing.