{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:53:25Z","timestamp":1791903205428,"version":"4.3.4"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,1,2]],"date-time":"2003-01-02T00:00:00Z","timestamp":1041465600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2003,1]]},"abstract":"Objective<\/jats:title>Our objective was to quantify the extent and time course of the effects of morphine\u20106\u2010glucuronide and morphine on pain threshold, pain tolerance, pupil diameter, and side effects.<\/jats:p><\/jats:sec>Methods<\/jats:title>In a double\u2010blind, placebo\u2010controlled, randomized, 3\u2010way crossover study, 12 healthy volunteers (6 men and 6 women) received 63 to 112 mg of morphine\u20106\u2010glucuronide or 26 to 66 mg of morphine as an intravenous bolus, followed by an infusion of the same medication for 1.8 to 6.4 hours. Analgesia was assessed every 30 minutes for up to 16 hours by means of transcutaneous electrical stimulation (sine wave, 5 Hz; intensity, 0\u20139.99 mA). Pupil diameter and side effects were recorded concomitantly.<\/jats:p><\/jats:sec>Results<\/jats:title>At the administered doses, morphine\u20106\u2010glucuronide and morphine had comparable effects on pain tolerance, pupil diameter, and side effects. The delay between the time course of the plasma concentrations and the time course of the effects was longer for morphine\u20106\u2010glucuronide than for morphine (transfer half\u2010life, 8.2 hours versus 2.6 hours for pain tolerance and 7.7 hours versus 2.8 hours for pupil diameter). The slope of the linear concentration versus effect relationship for pain tolerance was flatter for morphine\u20106\u2010glucuronide than for morphine (0.05% versus 0.6% increase in pain tolerance per nanomole per liter of morphine\u20106\u2010glucuronide and morphine at effect site, respectively). Morphine\u20106\u2010glucuronide was less potent than morphine in producing pupil constriction (mean concentration at half\u2010maximum effect, 745 nmol\/L versus 26.4 nmol\/L for morphine\u20106\u2010glucuronide and morphine, respectively). In carriers of the mutated G118<\/jats:italic> allele of the \u03bc\u2010opioid receptor, the potency of the pupil\u2010constricting effects of morphine\u20106\u2010glucuronide and morphine was significantly smaller, and carriers of the G118<\/jats:italic> allele reported less nausea and vomited less often after administration of morphine\u20106\u2010glucuronide.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Morphine\u20106\u2010glucuronide clearly produced analgesic effects in healthy volunteers. However, the high amounts of systemic morphine\u20106\u2010glucuronide needed to produce the same effects as morphine suggest that morphine\u20106\u2010glucuronide barely contributes to the central nervous opioid effects after administration of analgesic doses of morphine.<\/jats:p>Clinical Pharmacology & Therapeutics<\/jats:italic> (2003) 73<\/jats:bold>, 107\u2013121; doi: 10.1067\/mcp.2003.5<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2003.5","type":"journal-article","created":{"date-parts":[[2003,2,11]],"date-time":"2003-02-11T16:25:29Z","timestamp":1044980729000},"page":"107-121","source":"Crossref","is-referenced-by-count":175,"title":["Analgesic effects of morphine and morphine\u20106\u2010glucuronide in a transcutaneous electrical pain model in healthy volunteers"],"prefix":"10.1111","volume":"73","author":[{"given":"Carsten","family":"Skarke","sequence":"first","affiliation":[{"name":"pharmazentrum frankfurt<\/i>, Institute of Clinical Pharmacology Johann Wolfgang Goethe University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Darimont","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt<\/i>, Institute of Clinical Pharmacology Johann Wolfgang Goethe University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Schmidt","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt<\/i>, Institute of Clinical Pharmacology Johann Wolfgang Goethe University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Geisslinger","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt<\/i>, Institute of Clinical Pharmacology Johann Wolfgang Goethe University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"L\u00f6tsch","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt<\/i>, Institute of Clinical Pharmacology Johann Wolfgang Goethe University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,1,2]]},"container-title":["Clinical Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2003.5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T19:20:52Z","timestamp":1700162452000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2003.5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1067\/mcp.2003.5"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2003.5","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}