Formula C23H27NO9 | Molar mass 461.46 g/mol | |
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Morphine-6-glucuronide (M6G) is a major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine and heroin - M6G is formed from morphine by the enzyme UDP-Glucuronosyltransferase-2B7 (UGT2B7). M6G can accumulate to toxic levels in kidney failure.
History of discovery
This analgesic 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 HPLC 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 renal failure, which resolved as kidney 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.