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Morphine-6-glucuronide (M6G) is a major active
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of
morphine Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...
. M6G is formed from morphine by the enzyme UGT2B7. It has analgesic effects roughly half that of morphine. M6G can accumulate to toxic levels in kidney failure.


History of discovery

This
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
activity of M6G (in animals) was first noted by Yoshimura. Subsequent work at St Bartholomew's Hospital, London in the 1980s, using a sensitive and specific high-performance liquid chromatography assay, accurately defined for the first time the metabolism of morphine, and the abundance of this metabolite (along with morphine-3-glucuronide, considered an inactive metabolite). It was postulated that kidney impairment would result in accumulation of the kidney-excreted active agent M6G, leading to potentially fatal toxicity such as respiratory depression. The frequent use of morphine in critically ill patients, and the common occurrence of kidney failure in this group implied that M6G accumulation could be a common, but previously unanticipated problem. The first studies demonstrated massive levels of M6G in 3 patients with kidney failure, which resolved as
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
function returned. Accumulation of M3G and M6G also decreased with return of kidney function after kidney transplantation. A key step in defining the importance of M6G in humans came in 1992 when the substance was artificially synthesised and administered to patients with pain, the majority of whom described pain relief.


See also

* Codeine-6-glucuronide * Morphine-N-oxide


References

{{Opioidergics 4,5-Epoxymorphinans Mu-opioid receptor agonists Opioid metabolites Glucuronide esters Hydroxyarenes