TY - JOUR T1 - Antagonist effects of nalbuphine in opioid-dependent human volunteers. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 929 LP - 937 VL - 248 IS - 3 AU - K L Preston AU - G E Bigelow AU - I A Liebson Y1 - 1989/03/01 UR - http://jpet.aspetjournals.org/content/248/3/929.abstract N2 - The subjective, physiological and behavioral effects of nalbuphine, an opioid mixed agonist/antagonist analgesic, naloxone and hydromorphone were studied on adult, male, methadone-dependent volunteers living on a clinical research ward. The purpose was to assess nalbuphine's agonist properties vs. antagonist properties relative to a standard agonist (hydromorphone) and a standard antagonist (naloxone) in opioid-dependent subjects. Drug conditions included saline placebo, nalbuphine hydrochloride (0.375, 0.75, 1.5, 3 and 6 mg), naloxone hydrochloride (0.1 and 0.2 mg) and hydromorphone hydrochloride (4 and 8 mg). Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5 hr experimental sessions. Physiologic measures were monitored continuously before and for 2 hr after drug administration: pupil diameter and subject- and observer-rated behavioral responses were measured intermittently over this same period. Hydromorphone increased ratings significantly on subjective measures typical of morphine-like effects. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Nalbuphine produced effects which were qualitatively similar to the effects of naloxone and showed no evidence of opioid agonist effects in these methadone-dependent subjects. The withdrawal syndrome precipitated by nalbuphine was indistinguishable from that produced by naloxone. ER -