Morphine-6-glucuronide - An analgesic of the future?

Citation
J. Lotsch et G. Geisslinger, Morphine-6-glucuronide - An analgesic of the future?, CLIN PHARMA, 40(7), 2001, pp. 485-499
Citations number
128
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOKINETICS
ISSN journal
0312-5963 → ACNP
Volume
40
Issue
7
Year of publication
2001
Pages
485 - 499
Database
ISI
SICI code
0312-5963(2001)40:7<485:M-AAOT>2.0.ZU;2-#
Abstract
Morphine-6-beta -glucuronide (M6G) is an opioid agonist that plays a role i n the clinical effects of morphine. Although M6G probably crosses the blood -brain barrier with difficulty, during long term morphine administration it [nay reach sufficiently high CNS concentrations to exert clinically releva nt opioid effects. As a consequence of its almost exclusive renal eliminati on, M6G may accumulate in the body of patients with impaired renal function and cause severe opioid adverse effects with insidious onset and long pers istence. Its profile of receptor affinities, however, gives reason to speculate that M6G may exhibit analgesic effects while causing fewer adverse effects than morphine, This is supported by reports of the good tolerability of intrath ecal and intravenous injections of M6G in humans with intact renal function . M6G may thus be contemplated as an analgesic for short term postoperative analgesia, especially for intrathecal analgesic therapy. In addition, its possibly higher potency than morphine makes M6G a candidate opioid for loca l or peripheral analgesic therapy. However, current knowledge is too incomp lete to finally judge the clinical usefulness of M6G. The next topics for c linical research on M6G should include: (i) a comparison of the potencies o f M6G and morphine to cause wanted and unwanted clinical effects; (ii) deve lopment of a predictive population pharmacokinetic-pharmacodynamic model of M6G with calculation of the transfer half-life between plasma and effect s ite; and (ii) identification of cofactors influencing the action of M6G tha t can serve as predictors for the clinical outcome of morphine/M6G therapy in an individual including the pharmacogenetics of M6G.