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Clin Pharmacol Ther. 2001 Jan;69(1):66-71.

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

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Department of Anesthesiology, Virginia Mason Medical Center, The University of Washington, Seattle 98111, USA.


ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively 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 placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x 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 measured. 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 selective peripheral opioid anitagonism without affecting central opioid analgesia.

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