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Morphine-6-glucuronide (M6G) is the major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine (and thus heroin and codeine). This analgesic activity of M6G (in animals) was first noted by Yoshimura.
Subsequent work at St Bartholomew's Hospital, London in the 1980's, 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 two other major, but pharmacologically inactive metabolites, morphine-3-glucuronide and morphine-3,6-diglucuronide).
It was postulated that renal impairment would result in accumulation of the renally-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 renal 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. Subsequent work formally examined the role of renal function in the pharmacokinetics of morphine and its metabolites by studying their behaviour before and after renal transplantation.
A key step in defining the importance of M6G in man came in 1992 when the substance was artificially synthesised and administered to patients with pain, the majority of whom described pain relief.
CAS# 20290-10-2; 28932-95-8; 32205-91-7; 155755-06-9
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Morphine-6-glucuronide". A list of authors is available in Wikipedia.|