Morphine-6-glucuronide (M6G) is a major active metabolite of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

. M6G is formed from morphine by the enzyme

UGT2B7 UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltrans ...

. It has analgesic effects more potent than morphine. M6G can accumulate to toxic levels in

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

History of discovery

This analgesic activity of M6G (in animals) was first noted by Yoshimura. Subsequent work at

St Bartholomew's Hospital St Bartholomew's Hospital, commonly known as Barts, is a teaching hospital located in the City of London. It was founded in 1123 and is currently run by Barts Health NHS Trust. History Early history Barts was founded in 1123 by Rahere (die ...

, 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 Morphine-3-glucuronide is a metabolite of morphine produced by UGT2B7. It is not active as an opioid receptor, opioid agonist, but does have some action as a convulsant, which does not appear to be mediated through opioid receptors, but rather th ...

, 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

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 The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

function returned. Accumulation of M3G and M6G also decrease 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.

References

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

History of discovery

See also

References