当前位置： SCI文献检索 > ANESTHESIOLOGY期刊下所有文献 > Lack of analgesic activity of morphine-6-glucuronide after short-term intravenous administration in healthy volunteers.

Lack of analgesic activity of morphine-6-glucuronide after short-term intravenous administration in healthy volunteers.

Abstract：

BACKGROUND:The analgesic activity of morphine-6-glucuronide (M-6-G) is well recognized for its contribution to the effects of morphine and its possible use as an opioid analgesic with a wider therapeutic range than morphine. The present study attempted to quantify the relative contribution of M-6-G to analgesia observed after systemic administration of morphine. METHODS:In a placebo-controlled, sixfold crossover study in 20 healthy men, the effects of M-6-G were assessed at steady-state plasma concentrations of M-6-G identical to and two and three times higher than those measured after administration of morphine. Morphine and M-6-G were administered as an intravenous bolus followed by infusion over 4 h. Dosage A was M-6-G-bolus of 0.015 mg/kg plus infusion of 0.0072 mg x kg(-1) x h(-1). Dosage B was M-6-G-bolus of 0.029 mg/kg plus infusion of 0.014 mg x kg(-1) x h(-1). Dosage C was M-6-G-bolus of 0.044 mg/kg plus infusion of 0.022 mg x kg(-1) x h(-1). Dosage D was a morphine bolus of 0.14 mg/kg plus infusion of 0.05 mg x kg(-1) x h(-1) for 4 h. Dosage E was M-6-G combined with morphine (doses A + D). Dosage F was a placebo. The analgesic effects of M-6-G and morphine were measured before administration of the bolus and after 3.5 h using an experimental pain model based on pain-related cortical potentials and pain ratings after specific stimulation of the nasal nociceptor with short pulses of gaseous carbon dioxide. RESULTS:Morphine significantly reduced subjective and objective pain correlates compared with placebo. In contrast, M-6-G produced no statistically significant effects. The addition of M-6-G to morphine did not increase the effects of morphine. Morphine produced significantly more side effects than M-6-G. CONCLUSION:After short-term intravenous administration at doses that produce plasma concentrations of M-6-G similar to those seen after administration of morphine, M-6-G had no analgesic effects in the present placebo-controlled study in healthy volunteers.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Lötsch J,Kobal G,Stockmann A,Brune K,Geisslinger G

doi

10.1097/00000542-199712000-00014

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

1348-58

issue

eissn

0003-3022

issn

1528-1175

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

在线工具

Lack of analgesic activity of morphine-6-glucuronide after short-term intravenous administration in healthy volunteers.