Morphine-3-glucuronide

Morphine-3-glucuronide
Names
	IUPAC name 6α-Hydroxy-17-methyl-7,8-didehydro-4,5α-epoxymorphinan-3-yl β-D-glucopyranosiduronic acid
	Systematic IUPAC name (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-{[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methano[1]benzofuro[3,2-e]isoquinolin-9-yl]oxy}oxane-2-carboxylic acid
Identifiers
CAS Number	20290-09-9 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL1329 ;
ChemSpider	4588593 ;
MeSH	Morphine-3-glucuronide
PubChem CID	5484731;
UNII	O27Z9CH39A ;
CompTox Dashboard (EPA)	DTXSID80174157 ;
	InChI InChI=1S/C23H27NO9/c1-24-7-6-23-10-3-4-12(25)20(23)32-18-13(5-2-9(14(18)23)8-11(10)24)31-22-17(28)15(26)16(27)19(33-22)21(29)30/h2-5,10-12,15-17,19-20,22,25-28H,6-8H2,1H3,(H,29,30)/t10-,11+,12-,15-,16-,17+,19-,20-,22+,23-/m0/s1 Key: WAEXKFONHRHFBZ-ZXDZBKESSA-N ;
	SMILES O=C(O)[C@H]6O[C@@H](Oc2c1O[C@H]5[C@@H](O)\C=C/[C@H]4[C@@H]3N(C)CC[C@@]45c1c(cc2)C3)[C@H](O)[C@@H](O)[C@@H]6O;
Properties
Chemical formula	C23H27NO9
Molar mass	461.462 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Morphine-3-glucuronide is a metabolite of morphine produced by UGT2B7.^[1] It is not active as an opioid agonist,^[2] but does have some action as a convulsant, which does not appear to be mediated through opioid receptors,^[3] but rather through interaction with glycine and/or GABA receptors. As a polar compound, it has a limited ability to cross the blood–brain barrier, but kidney failure may lead to its accumulation and result in seizures. Probenecid and inhibitors of P-glycoprotein can enhance uptake of morphine-3-glucuronide and, to a lesser extent, morphine-6-glucuronide.^[4] Reported side effects related to the accumulation of this metabolite include convulsions, agitation, hallucinations, hyperalgesia, and coma.

Formation

The enzyme UDP-Glucuronosyltransferase-2B7 converts morphine to its glucuronide by adding a sugar acid at the phenolic hydroxy group, with uridine diphosphate (UDP) as byproduct:^[1]

^ ^a ^b Coffman BL, Rios GR, King CD, Tephly TR (1 January 1997). "Human UGT2B7 catalyzes morphine glucuronidation". Drug Metab. Dispos. 25 (1): 1–4. PMID 9010622. Archived from the original on 29 September 2007. Retrieved 30 March 2018.
^ Vindenes V, Ripel A, Handal M, Boix F, Mørland J (July 2009). "Interactions between morphine and the morphine-glucuronides measured by conditioned place preference and locomotor activity". Pharmacology Biochemistry and Behavior. 93 (1): 1–9. doi:10.1016/j.pbb.2009.03.013. PMID 19351545. S2CID 5328449.
^ Hemstapat K, Le L, Edwards SR, Smith MT (July 2009). "Comparative studies of the neuro-excitatory behavioural effects of morphine-3-glucuronide and dynorphin a(2-17) following spinal and supraspinal routes of administration". Pharmacology Biochemistry and Behavior. 93 (4): 498–505. doi:10.1016/j.pbb.2009.06.016. PMID 19580825. S2CID 207331030.
^ Bertram G. Katzung; Susan B. Masters; Anthony J. Trevor. Basic & Clinical Pharmacology (11th ed.).