View source for Morphine-6-glucuronide

{{chembox
|ImageFile=Morphine 6-glucuronide.png
|ImageSize=200px
|IUPACName=
|OtherNames=M6G
|Section1= {{Chembox Identifiers
|  CASNo=20290-10-2
|  PubChem=5360621
|  SMILES=CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)O)O[C@H]3[C@H](C=C4)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)C(=O)O)O)O)O
|  MeSHName=Morphine-6-glucuronide
  }}
|Section2= {{Chembox Properties
|  Formula=C<sub>23</sub>H<sub>27</sub>NO<sub>9</sub>
|  MolarMass=461.46 g/mol
|  Appearance=
|  Density=
|  MeltingPt=
|  BoilingPt=
|  Solubility=
  }}
|Section3= {{Chembox Hazards
|  MainHazards=
|  FlashPt=
|  Autoignition=
  }}
}}

'''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>{{cite journal | title = Metabolism of drugs. LXII. Isolation and identification of morphine glucuronides in urine and bile of rabbits | journal = Biochem Pharmacol | year = 1969 | volume = 18 | pages = 279–86 | doi = 10.1016/0006-2952(69)90205-6 | author = Hidetoshi, Y | pmid = 5778147 | last2 = Oguri | first2 = K | last3 = Tsukamoto | first3 = H | issue = 2}}</ref>

Subsequent work at [[St Bartholomew's Hospital]], London in the 1980s,<ref>{{Cite journal | doi = 10.1038/clpt.1990.2 | title = Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide | journal = Clin Pharmacol Ther. | year = 1990 | volume = 47 | pages = 12–9 | pmid = 2295214 | last1 = Osborne | first1 = R | last2 = Joel | first2 = S | last3 = Trew | first3 = D | last4 = Slevin | first4 = M | issue = 1}}</ref> using a sensitive and specific [[High performance liquid chromatography|HPLC assay]],<ref>{{cite journal | title = An improved method for the simultaneous determination of morphine and its principal glucuronide metabolites| journal = J Chromatogr| year = 1988 | volume = 430 | pages = 394–9 | doi = 10.1016/S0378-4347(00)83176-X | author = Joel, S | pmid = 3235512 | last2 = Osborne | first2 = RJ | last3 = Slevin | first3 = ML | issue = 2}}</ref> accurately defined for the first time the metabolism of morphine, and the abundance of this metabolite (along with [[morphine-3-glucuronide]]<ref>[http://dmd.aspetjournals.org/cgi/content/abstract/19/6/1087 ''Renal tubular transport of morphine, morphine-6-glucuronide, and morphine-3-glucuronide in the isolated perfused rat kidney.'' JT Van Crugten, BC Sallustio, RL Nation and AA Somogyi. Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia. ]</ref> and morphine-3,6-diglucuronide, both considered inactive metabolites).

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>{{cite journal | title = Morphine intoxication in renal failure: the role of morphine-6-glucuronide | journal = Br Med J | year = 1986 | volume = 292 | pages = 1548–9 | doi = 10.1136/bmj.292.6535.1548 | author = Osborne, R J | pmid = 3087512 | last2 = Joel | first2 = SP | last3 = Slevin | first3 = ML | issue = 6535 | pmc = 1340555}}</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>{{cite journal | doi = 10.1038/clpt.1993.127 | title = The pharmacokinetics of morphine and morphine glucuronides in kidney failure | journal = Clin Pharmacol Ther | year = 1993 | volume = 54 | pages = 158–67 | pmid = 8354025 | last1 = Osborne | first1 = R | last2 = Joel | first2 = S | last3 = Grebenik | first3 = K | last4 = Trew | first4 = D | last5 = Slevin | first5 = M | issue = 2}}</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>{{cite journal | title = The analgesic activity of morphine-6-glucuronide | journal = Br J Clin Pharmacol | year = 1992 | volume = 34 | pages = 130–8 | pmid = 1419474 | last1 = Osborne | first1 = R | last2 = Thompson | first2 = P | last3 = Joel | first3 = S | last4 = Trew | first4 = D | last5 = Patel | first5 = N | last6 = Slevin | first6 = M | issue = 2 | pmc = 1381529}}</ref>

The mu-3 receptor substype is further evidenced to be activated (agonized) by morphine-6β-glucuronide but not morphine itself.<ref>{{cite journal |author=Brown GP, Yang K, King MA, ''et al'' |title=3-Methoxynaltrexone, a selective heroin/morphine-6beta-glucuronide antagonist |journal=FEBS Lett. |volume=412 |issue=1 |pages=35–8 |year=1997 |month=July |pmid=9257684 |doi=10.1016/S0014-5793(97)00710-2 |url=}}</ref> This finding is also true of certain heroin metabolites (6-MAM) but not morphine proper.

==References==
{{reflist}}

{{Opioids}}

[[Category:Glycosides]]
[[Category:Opioids]]
[[Category:Morphinans]]
[[Category:Phenols]]

[[ru:Морфин-6-глюкуронид]]
[[Category:2Fix]]