Nalbuphine is a mixed opioid agonist/antagonist analgesic. It labels mu receptors most potently where it acts as an antagonist. Nalbuphine is analgesic in the tail-flick assay after systemic (ED50, 41.8 mg/kg s.c.), i.c.v. (ED50, 21.3 μg) or intrathecal administration (ED50, 11.2 μg). Analgesia elicited by systemic nalbuphine was reversed by nor- binaltorphimine, but not by β-funaltrexamine or naltrindole despite their ability to antagonize morphine and [D-Pen2, D-Pen5]enkephalin analgesia, respectively. This insensitivity toward β-funaltrexamine and naltrindole argued strongly against either a mu or delta component of analgesia. Nor- binaltorphimine antagonized systemic nalbuphine analgesia over 10-fold more potently after intrathecal injection of the antagonist than after i.c.v. administration, implying a role for kappa1 receptors at the spinal level. The presence of analgesic cross-tolerance between nalbuphine and both naloxone benzoylhydrazone and nalorphine indicated an analgesic role for kappa3 receptors, which act supraspinally. Additional studies revealed synergistic interactions between spinal kappa1 and supraspinal kappa3 receptors when nalbuphine was given both intrathecally and i.c.v. In conclusion, these studies suggest that nalbuphine elicits analgesia through a complex interaction of supraspinal kappa3 and spinal kappa1 mechanisms.
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1992|