Antagonist effects of nalbuphine in opioid-dependent human volunteers.
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.
Preston
K L
KL
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bigelow
G E
GE
Liebson
I A
IA
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008297:Male; D008691:Methadone; D009019:Morphinans / Q000494:pharmacology*; D009266:Nalbuphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced
D009019:Morphinans; D009270:Naloxone; D009266:Nalbuphine; D004091:Hydromorphone; D008691:Methadone