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.
Kamei
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Saitoh
A
A
Suzuki
T
T
Misawa
M
M
Nagase
H
H
Kasuya
Y
Y
D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002047:Buprenorphine / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000633:toxicity; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D000996:Antitussive Agents; D011957:Receptors, Opioid; D002047:Buprenorphine; D002211:Capsaicin