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ADL 8‐2698, a trans‐3,4‐dimethyl‐4‐ (3‐hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia
Author(s) -
Liu Spencer S.,
Hodgson Peter S.,
Carpenter Randall L.,
Fricke James R.
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2001.112680
Subject(s) - morphine , placebo , anesthesia , medicine , opioid , receptor , alternative medicine , pathology
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 · kg −1 ), and oral ADL 8–2698 (4 mg) and 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 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 antagonism without affecting central opioid analgesia. Clinical Pharmacology & Therapeutics (2001) 69 , 66–71; doi: 10.1067/mcp.2001.112680