ADL 8-2698, a trans-3,4-dimethyl-4(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia

ADL-8-2698 is a novel peripherally restricted opioid antagonist that may se lectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral place bo and intravenous morphine (0.05 mg.kg(-1)), and oral ADL 8-2698 (4 mg) an d intravenous morphine (0.05 mg.kg(-1)) in a double blind, cross-over study . Morphine prolonged gastrointestinal transit time from 69 to 103 minutes ( P = .005); this was prevented by ADL 8-2698 (P = .004), Postoperatively, 45 patients were randomly assigned in a double-blind fashion to receive ADL 8 -2698 (4 mg) or placebo and intravenous morphine (0.15 mg/kg) or to receive oral and intravenous placebo. Analgesia and pupil constriction were measur ed. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002), We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of se lective peripheral opioid antagonism without affecting central opioid analg esia.