Proglumide potentiates morphine analgesia for acute postsurgical pain

Proglumide, an antagonist of cholecystokinin, has been shown to potentiate morphine analgesia in animal and human experimental pain models. This study was undertaken to determine whether proglumide enhances morphine analgesia for patients experiencing postoperative pain. At onset of pain after the removal of impacted third molars, patients (n = 60) received intravenously either 4 mg morphine, 8 mg morphine, or 4 mg morphine plus proglumide (0.05, 0.5, or 5 mg). The administration of 8 mg morphine significantly reduced pain, in comparison with baseline and 4 mg morphine, for the first 30 minutes. The addition of 0.05 mg proglumide resulted in a significant increase in the magnitude and duration of the analgesic activity of 4 mg morphine; 0.5 and 5.0 mg proglumide did not produce this effect. No difference was seen in respiratory rate or in the frequency of side effects among the various forms of treatment. These data indicate that a low dose of proglumide potentiates both the magnitude and the duration of morphine analgesia in a clinical model of acute pain, without any detectable increase in side effects.