RT Journal Article SR Electronic T1 Relative Efficacy of Buprenorphine, Nalbuphine and Morphine in Opioid-Treated Rhesus Monkeys Discriminating Naltrexone JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1167 OP 1173 DO 10.1124/jpet.103.051425 VO 306 IS 3 A1 Stacy L. Sell A1 Lance R. McMahon A1 Charles P. France YR 2003 UL http://jpet.aspetjournals.org/content/306/3/1167.abstract AB Efficacy is one determinant of whether a drug is an agonist or an antagonist under a particular set of conditions. Relative efficacy among the μ opioid receptor (MOR) ligands buprenorphine, nalbuphine, and morphine was examined in monkeys dependent on morphine (3.2 mg/kg/day) or l-α-acetylmethadol (LAAM) (1.0 mg/kg twice daily) and that discriminated naltrexone (0.0178 mg/kg) from saline. In morphine-treated monkeys, buprenorphine and not nalbuphine substituted for naltrexone. When administered before naltrexone in morphine-treated monkeys, morphine and nalbuphine shifted the naltrexone dose-effect curve to the right, while buprenorphine shifted the naltrexone dose-effect curve to the left. Under conditions of acute morphine deprivation, naltrexone-lever responding was slightly attenuated by buprenorphine and markedly attenuated by nalbuphine and morphine. In LAAM-treated monkeys, buprenorphine substituted completely for naltrexone in only one monkey, while nalbuphine and morphine failed to substitute in any monkey. When administered before naltrexone in LAAM-treated monkeys, buprenorphine, nalbuphine, and morphine dose dependently shifted the naltrexone dose-effect curve to the right, with the exception of one monkey in which buprenorphine shifted the naltrexone dose-effect curve to the left. These results demonstrate that a low efficacy MOR ligand can exert agonist or antagonist actions in the same animal depending on immediate pharmacologic history. The qualitatively different effects of buprenorphine in morphine- and LAAM-treated monkeys might be related to magnitude of dependence insofar as dependence can determine the efficacy required for agonist activity. Thus, buprenorphine has markedly different effects across different levels of opioid dependence. The American Society for Pharmacology and Experimental Therapeutics