Acute effects of pentazocine, naloxone and morphine in opioid-dependent volunteers.

The purpose of this study was to evaluate the agonist and antagonist properties of pentazocine, an opioid mixed agonist-antagonist analgesic, in relation to prototypic opioid agonist and antagonist drugs in opioid-dependent human subjects. Pentazocine (45 and 60 mg), naloxone (0.1 and 0.2 mg), morphine (20, 40 and 60 mg) and saline placebo were administered intramuscularly to six male volunteers maintained on methadone (30 mg/24 hr p.o.), following a double-blind, randomized block order design. Drugs were administered 20 hr after the last dose of methadone. Subject-reported effects and physiological measures were collected before drug administration and during 4 hr postadministration. Morphine produced significant dose-related increases in subjective measures characteristic of mu agonist effects, decreased pupil diameter and was classified as an opioid agonist. Naloxone precipitated a dose-related opioid withdrawal syndrome which was measurable on several subject-rated measures, and significantly increased pupil diameter. Subjects consistently identified naloxone as an antagonist. Pentazocine precipitated a withdrawal syndrome, but the effects were not dose-dependent, and produced symptoms of confusion and dysphoric changes that were not observed after naloxone administration. Pentazocine was classified as an antagonist by some individuals, and as alcohol or hallucinogen by others. The results of the present study indicate that pentazocine acts in humans as a partial mu agonist with a non-mu component of activity.