THE ANTINOCICEPTIVE POTENCIES OF OXYCODONE, NOROXYCODONE AND MORPHINEAFTER INTRACEREBROVENTRICULAR ADMINISTRATION TO RATS

The antinociceptive activity of noroxycodone (NOR) was determined and its potency compared with that of oxycodone (OXY) and morphine (MOR) a fter intracerebroventricular (icv) administration to Sprague-Dawley ra ts. 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 admi nistration 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 e ffects of NOR (332 nmol icv) and MOR (93 nmol icv) indicating the invo lvement of opioid receptors in the antinociceptive activities of NOR a nd MOR. NOR, administered by the icv route, also produced excitatory e ffects throughout the antinociceptive dose range, the severity of whic h was reduced but not abolished by prior administration of naloxone (5 5 nmol icv). As excitatory effects have not been observed in patients receiving OXY, it is unlikely that NOR contributes to the analgesic ac tivity of OXY administered systemically to humans.