ArticlesThe intrinsic antinociceptive effects of oxycodone appear to beκ-opioid receptor mediatedRoss, Fraser B; Smith, Maree T*Author Information School of Pharmacy, Steele Building, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia *Corresponding author. Tel.: +61 7 33652554; fax: +61 7 33651688; e-mail: [email protected] Submitted December 20, 1996; revised May 20, 1997; accepted June 26, 1997. Pain: November 1997 - Volume 73 - Issue 2 - p 151-157 doi: 10.1016/S0304-3959(97)00093-6 Buy Metrics Abstract Our previous studies in the Sprague–Dawley rat showed that the intrinsic antinociceptive effects of oxycodone are naloxone reversible in a manner analogous to morphine but that in contrast to morphine, oxycodone's antinociceptive effects have a rapid onset of maximum effect (≈5–7 min compared to 30–45 min for morphine), comprise one antinociceptive phase (compared to two phases) and are of relatively short duration (≈90 min compared to ≈180 min). In the present study, administration of a range of selective opioid receptor antagonists has shown that the intrinsic antinociceptive effects of oxycodone (171 nmol) are not attenuated by i.c.v. administration of (i) naloxonazine, a μ1-selective opioid receptor antagonist, or (ii) naltrindole, a δ-selective opioid receptor antagonist, in doses that completely attenuated the intrinsic antinociceptive effects of equipotent doses of the respective μ- and δ-opioid agonists, morphine and enkephalin-[d-Pen2,5] (DPDPE). Although β-funaltrexamine (β-FNA) attenuated the antinociceptive effects of oxycodone (171 nmol i.c.v.), it also attenuated the antinociceptive effects of morphine and bremazocine (κ-opioid agonist) indicative of non-selective antagonism. Importantly, the antinociceptive effects of oxycodone (171 nmol i.c.v.) were markedly attenuated by the prior i.c.v. administration of the selective κ-opioid receptor antagonist, norbinaltorphimine (nor-BNI), in a dose (0.3 nmol) that did not attenuate the antinociceptive effects of an equipotent dose of i.c.v. morphine (78 nmol). Taken together, these data strongly suggest that the intrinsic antinociceptive effects of oxycodone are mediated by κ-opioid receptors, in contrast to morphine which interacts primarily with μ-opioid receptors. © Lippincott-Raven Publishers.