The analgesic effect of nalbuphine and its long-acting prodrug, nalbuphine pivalate, in rats.

Background: Nalbuphine is an opioid-analgesic with agonist-antagonist properties. Recently, we have synthesized a nalbuphine prodrug, nalbuphine pivalate. The aim of the present study was to evaluate the analgesic effect and the analgesic duration of this prodrug.

Methods: Forty-eight male Sprague-Dawley rats (4 groups, n = 12 in each group) were used. Rats in group 1 received nalbuphine HCl 25 mumol/kg (in saline) intramuscular injection; rats in group 2 received nalbuphine pivalate 25 mumol/kg (in sesame oil) intramuscular injection, whereas those in groups 3 and 4 received saline and sesame oil respectively. The analgesic effects of testing agents were evaluated using the cold ethanol tail-flick test (-30 degrees C).

Results: Both nalbuphine HCl and nalbuphine pivalate demonstrated significant analgesic effects. The analgesic duration of nalbuphine HCl was 2 h while that of nalbuphine pivalate was 30 h.

Conclusions: Nalbuphine pivalate has a very long duration of analgesic action. This fascinating finding is worth further evaluation.