Morphine-6-glucuronide
From DrugPedia: A Wikipedia for Drug discovery
| Morphine-6-glucuronide
| |
| Systematic (IUPAC) name | |
| N/A | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C23H27NO9 |
| Mol. mass | 461.46178 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
[edit] Description
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 thus heroin and codeine). This analgesic activity of M6G (in animals) was first noted by Yoshimura.<ref>Metabolism of drugs. LXII. Isolation and identification of morphine glucuronides in urine and bile of rabbits. Biochem Pharmacol. 1969;18:279-86</ref>
Subsequent work at St Bartholomew's Hospital, London in the 1980s,<ref>Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther. 1990;47:12-9</ref> using a sensitive and specific HPLC assay,<ref>An improved method for the simultaneous determination of morphine and its principal glucuronide metabolites. J Chromatogr. 1988;430:394-9</ref> accurately defined for the first time the metabolism of morphine, and the abundance of this metabolite (along with morphine-3-glucuronide, also an active metabolite, and morphine-3,6-diglucuronide, considered inactive).
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.<ref>Morphine intoxication in renal failure: the role of morphine-6-glucuronide. Br Med J. 1986;292:1548-9</ref> 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.<ref>The pharmacokinetics of morphine and morphine glucuronides in kidney failure. Clin Pharmacol Ther. 1993;54:158-67</ref>
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.<ref>The analgesic activity of morphine-6-glucuronide. Br J Clin Pharmacol. 1992;34:130-8</ref>
[edit] General Properties
*Molecular Weight
461.46178
*Molecular Formula
C23H27NO9
*IUPAC NAME
N/A
*Canonical Smiles
CN1CCC23C4C1CC5=C2C(=C(C=C5)O)OC3C(C=C4)OC6C(C(C(C(O6)C(=O)O)O)O)O
*Isomeric Smiles
CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)O)O[C@H]3C(C=C4)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)C(=O)O)O)O)O
*XLogP
-0.4
*Topological Polar Surface Area
149
