Abstract
The antinociceptive activity of noroxycodone (NOR) was determined and its potency compared with that of oxycodone (OXY) and morphine (MOR) after intracerebroventricular (icv) administration to Sprague-Dawley rats. The antinociceptive potencies of OXY and NOR relative to MOR were 0.44 and 0.17, respectively. Administration of naloxone (55 nmol icv) abolished the antinociceptive response produced by the subsequent administration of OXY (227 nmol icv), indicating that the antinociceptive effects of OXY are mediated by opioid receptors. In addition, the same dose of naloxone (55 nmol icv) markedly reduced the antinociceptive effects of NOR (332 nmol icv) and MOR (93 nmol icv) indicating the involvement of opioid receptors in the antinociceptive activities of NOR and MOR. NOR, administered by the icv route, also produced excitatory effects throughout the antinociceptive dose range, the severity of which was reduced but not abolished by prior administration of naloxone (55 nmol icv). As excitatory effects have not been observed in patients receiving OXY, it is unlikely that NOR contributes to the analgesic activity of OXY administered systematically to humans.
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