PRECIPITATED WITHDRAWAL BY PENTAZOCINE IN METHADONE-MAINTAINED VOLUNTEERS

Pentazocine is a partial mu agonist opioid with one-half to one-sixth the parenteral analgesic potency of morphine. The purpose of this stud y was to characterize the effects of pentazocine in comparison to nalo xone (an opioid antagonist), hydromorphone (an opioid mu agonist) and saline in methadone-dependent volunteers by using the same experimenta l methods used previously in the study of the opioid analgesics bupren orphine, 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. Pha rmacological challenges consisted of a double-blind i.m. injection of: pentazocine (dose range 7.5-120 mg), hydromorphone (5 and 10 mg), nal oxone (0.1 and 0.2 mg) or saline. Injections were given 20 hr after th e last dose of methadone. Measures included physiological indices and self-reports and observer ratings of drug effects. Naloxone and hydrom orphone produced characteristic antagonist-like and agonist-like effec ts, respectively, on subjective, observer and physiological indices. P entazocine produced primarily antagonist-like effects, with higher dos es (> = 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 b utorphanol, the specific profile of effects produced by pentazocine di ffered from that produced by naloxone, suggesting non-mu effects may m odulate the mu effects of pentazocine.