title: Discrimination of butorphanol and nalbuphine in opioid-dependent humans.
abstract: The purpose of the study was to evaluate the agonist and antagonist stimulus properties of the mixed opioid agonist antagonists butorphanol and nalbuphine in opioid-dependent subjects. Opioid-dependent volunteers (methadone 30 mg/day, PO) were trained in a three-choice drug discrimination procedure to discriminate between the effects of saline (2 ml), hydromorphone (10 mg/70 kg) and naloxone (0.15 mg/70 kg) administered IM. Subjects earned monetary reinforcement for correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were also collected. Hydromorphone and naloxone increased drug-appropriate responses and other characteristic subjective effects measures. Butorphanol and nalbuphine produced increases in naloxone-appropriate discrimination responding and in those subjective effect measures increased by naloxone. Butorphanol produced greater than 80% naloxone-appropriate responding at 1.05 mg/70 kg; nalbuphine produced 100% naloxone-appropriate responding at 2.1 mg/70 kg. Neither butorphanol nor nalbuphine showed opioid agonist-like effects in these subjects maintained at moderate levels of physical dependence. In opioid-dependent subjects, the stimulus effects of butorphanol and nalbuphine are antagonist-like.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Francis Scott Key Medical Center, Baltimore, MD 21224.
authors.forename: K L
authors.initials: KL
authors.lastname: Preston
authors.forename: G E
authors.initials: GE
authors.lastname: Bigelow
authors.forename: I A
authors.initials: IA
authors.lastname: Liebson
mesh_terms: D000328:Adult; D001519:Behavior / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002077:Butorphanol / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D005793:Generalization, Psychological / Q000187:drug effects; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008297:Male; D008691:Methadone / Q000494:pharmacology; D008875:Middle Aged; D009266:Nalbuphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*
chemical_list: D011957:Receptors, Opioid; D009270:Naloxone; D009266:Nalbuphine; D004091:Hydromorphone; D002077:Butorphanol; D008691:Methadone