Buprenorphine exerts its antinociceptive activity via mu 1-opioid receptors.

The mechanism of the antinociceptive effect of buprenorphine was assessed by administering selective mu-, mu1--, delta- and kappa-opioid receptor antagonists in mice. Intraperitoneal administration of buprenorphine, at doses of 0.3 to 3 mg/kg, produced dose-dependent antinociception in the tail-flick test. The antinociceptive activity of buprenorphine did not result from the activation of kappa- or delta-opioid receptors, since treatment with either nor-binaltorphimine, a selective kappa-opioid receptor antagonist, or naltrindole, a selective delta-opioid receptor antagonist, was completely ineffective in blocking buprenorphine-induced antinociception. However, the antinociceptive effect of buprenorphine was significantly antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Moreover, selective mu1-opioid receptor antagonist, naloxonazine and naltrexonazine, also significantly antagonized the antinociceptive effect of buprenorphine. Co-administration of kappa- and delta-opioid receptor antagonist with the mu-opioid receptor antagonists had no significant effect on the antagonistic profiles of the mu-opioid receptor antagonists on the antinociceptive effect of buprenorphine. These results suggest that buprenorphine acts selectively at mu1-opioid receptors to induce antinociceptive effects in mice.