Opioid antagonist effects of dezocine in opioid-dependent humans

Dezocine is an opioid mu-partial agonist recently approved for use as an analgesic in the United States. This study characterized the relative agonist versus antagonist effects of dezocine in comparison to naloxone (an opioid antagonist), hydromorphone (an opioid mu-agonist), and placebo (saline solution) in opioid-dependent volunteers. In a residential laboratory, six volunteer male opioid abusers maintained on 30 mg/day oral methadone underwent pharmacologic challenges two to three times per week, 20 hours after the last dose of methadone. Challenges consisted of a double-blind intramuscular injection of dezocine (dose range, 7.5 to 60 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg), or saline solution. Measures included physiologic indexes, self-reports of drug effects, and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively. Dezocine acted as an opioid antagonist, precipitating a withdrawal syndrome only slightly different from that produced by naloxone. Dezocine's antagonist effects were not directly dose related, but peaked at intermediate doses and declined at higher doses.