Abstract

Pentazocine is a partial mu agonist opioid with one-half to one-sixth the parenteral analgesic potency of morphine. The purpose of this study was to characterize the effects of pentazocine in comparison to naloxone (an opioid antagonist), hydromorphone (an opioid mu agonist) and saline in methadone-dependent volunteers by using the same experimental methods used previously in the study of the opioid analgesics buprenorphine, butorphanol and nalbuphine. In a residential laboratory, five volunteer male opioid abusers, maintained on 30 mg p.o. of methadone daily, underwent pharmacological challenges 2 to 3 times per week. Pharmacological challenges consisted of a double-blind i.m. injection of: pentazocine (dose range 7.5-120 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg) or saline. Injections were given 20 hr after the last dose of methadone. Measures included physiological indices and self-reports and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively, on subjective, observer and physiological indices. Pentazocine produced primarily antagonist-like effects, with higher doses (> = 60 mg) producing significant elevations of visual analog scale ratings of Drug Effects, Bad Effects and Sick; of observer ratings of piloerection, restlessness and adjective scores of opioid withdrawal; as well as increases in blood pressure, heart rate and pupil diameter and decreases in skin temperature. Similar to the previous study of butorphanol, the specific profile of effects produced by pentazocine differed from that produced by naloxone, suggesting non-mu effects may modulate the mu effects of pentazocine.