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- W2034887368 abstract "Our objective was to quantify the extent and time course of the effects of morphine-6-glucuronide and morphine on pain threshold, pain tolerance, pupil diameter, and side effects.In a double-blind, placebo-controlled, randomized, 3-way crossover study, 12 healthy volunteers (6 men and 6 women) received 63 to 112 mg of morphine-6-glucuronide 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, 0-9.99 mA). Pupil diameter and side effects were recorded concomitantly.At the administered doses, morphine-6-glucuronide 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-6-glucuronide than for morphine (transfer half-life, 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-6-glucuronide than for morphine (0.05% versus 0.6% increase in pain tolerance per nanomole per liter of morphine-6-glucuronide and morphine at effect site, respectively). Morphine-6-glucuronide was less potent than morphine in producing pupil constriction (mean concentration at half-maximum effect, 745 nmol/L versus 26.4 nmol/L for morphine-6-glucuronide and morphine, respectively). In carriers of the mutated G118 allele of the mu-opioid receptor, the potency of the pupil-constricting effects of morphine-6-glucuronide and morphine was significantly smaller, and carriers of the G118 allele reported less nausea and vomited less often after administration of morphine-6-glucuronide.Morphine-6-glucuronide clearly produced analgesic effects in healthy volunteers. However, the high amounts of systemic morphine-6-glucuronide needed to produce the same effects as morphine suggest that morphine-6-glucuronide barely contributes to the central nervous opioid effects after administration of analgesic doses of morphine." @default.
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- W2034887368 date "2003-01-01" @default.
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- W2034887368 title "Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers" @default.
- W2034887368 doi "https://doi.org/10.1067/mcp.2003.5" @default.
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