Buprenorphine is a potent kappa-opioid receptor antagonist in pigeons and mice.
Buprenorphine was studied for its antagonist activity against the specific kappa-opioid agonist U-50,488H in pigeons responding under a multiple schedule of grain presentation and in mice in an antinociception test. U-50,488H decreased rates of responding of pigeons over the dose range (2.5-20 mg/kg i.m.). In the presence of 0.32 mg/kg of buprenorphine, the U-50,488H dose-effect curve was shifted to the right approximately two-fold. Buprenorphine alone (0.01-0.08 mg/kg s.c.) inhibited in mice the abdominal stretching induced by i.p. acetic acid. beta-Funaltrexamine pretreatment blocked the mu-like agonist analgesic effect of buprenorphine and revealed an antagonist action of buprenorphine against 2.5 mg/kg of U-50,488H over the same dose range that it produced antinociception at the mu-receptor. Thus, buprenorphine is a potent kappa-opioid receptor antagonist, producing the kappa-antagonist activity over the same dose range that it produces its mu-mediated partial agonist activity.
Leander
J D
JD
Central Nervous System Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D010856:Columbidae; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D012055:Reinforcement Schedule
D000700:Analgesics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D002047:Buprenorphine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine