title: ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Virginia Mason Medical Center, The University of Washington, Seattle 98111, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Liu
authors.forename: P S
authors.initials: PS
authors.lastname: Hodgson
authors.forename: R L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: J R
authors.initials: JR
authors.lastname: Fricke
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D008297:Male; D008964:Molar, Third / Q000601:surgery; D009020:Morphine / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000209:etiology; D010880:Piperidines / Q000627:therapeutic use*; D014081:Tooth Extraction / Q000009:adverse effects; D014095:Tooth, Impacted / Q000601:surgery
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; C419502:alvimopan; D009020:Morphine