Norbuprenorphine-3-glucuronide

Norbuprenorphine-3-glucuronide (N3G) is a major active metabolite of the opioid modulator buprenorphine.[1] It has affinity for the κ-opioid receptor (Ki = 300 nM) and the nociceptin receptor (Ki = 18 μM), but not for the μ- or δ-opioid receptors.[1] Whether N3G acts as an agonist or antagonist of each of the former two respective sites has yet to be determined.[2] In animals, N3G has been found to produce sedation, decreased locomotion, and a small amount of antinociception, properties which are consistent with the effects of κ-opioid receptor agonists.[1] In addition, N3G has been found to reduce tidal volume but not respiratory rate.[1] Unlike norbuprenorphine, but similarly to buprenorphine and buprenorphine-3-glucuronide, N3G is not a substrate for P-glycoprotein.[2] However, due to its highly hydrophilic nature, N3G nonetheless passes the blood-brain-barrier in only very small amounts.[2]

Norbuprenorphine-3-glucuronide
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • (5β,7β)-7-[(2R)-2-Hydroxy-3,3-dimethyl-2-butanyl]-6-methoxy-18,19-dihydro-4,5-epoxy-6,14-ethenomorphinan-3-yl (5ξ)-β-D-lyxo-hexopyranosiduronic acid
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard100.230.712
Chemical and physical data
FormulaC31H43NO10
Molar mass589.682 g·mol−1
3D model (JSmol)
SMILES
  • C[C@]([C@H]1C[C@@]23CC[C@@]1([C@H]4[C@@]25CCN[C@@H]3Cc6c5c(c(cc6)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)C(=O)O)O)O)O)O4)OC)(C(C)(C)C)O
InChI
  • InChI=1S/C31H43NO10/c1-27(2,3)28(4,38)16-13-29-8-9-31(16,39-5)26-30(29)10-11-32-17(29)12-14-6-7-15(22(42-26)18(14)30)40-25-21(35)19(33)20(34)23(41-25)24(36)37/h6-7,16-17,19-21,23,25-26,32-35,38H,8-13H2,1-5H3,(H,36,37)/t16-,17-,19+,20+,21-,23+,25-,26-,28+,29-,30+,31-/m1/s1
  • Key:OOLGGESLZHGXGC-TXYLTYGDSA-N

See also
  • Morphine-3-glucuronide

References
  1. Brown SM, Holtzman M, Kim T, Kharasch ED (December 2011). "Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active". Anesthesiology. 115 (6): 1251–60. doi:10.1097/ALN.0b013e318238fea0. PMC 3560935. PMID 22037640.
  2. Brown SM, Campbell SD, Crafford A, Regina KJ, Holtzman MJ, Kharasch ED (October 2012). "P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception". J. Pharmacol. Exp. Ther. 343 (1): 53–61. doi:10.1124/jpet.112.193433. PMC 3464040. PMID 22739506.


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