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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H27NO9
Molecular Weight 461.4618
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MORPHINE-6-GLUCURONIDE

SMILES

CN1CC[C@]23[C@H]4OC5=C(O)C=CC(C[C@@H]1[C@@H]2C=C[C@@H]4O[C@@H]6O[C@@H]([C@@H](O)[C@H](O)[C@H]6O)C(O)=O)=C35

InChI

InChIKey=GNJCUHZOSOYIEC-GAROZEBRSA-N
InChI=1S/C23H27NO9/c1-24-7-6-23-10-3-5-13(31-22-17(28)15(26)16(27)19(33-22)21(29)30)20(23)32-18-12(25)4-2-9(14(18)23)8-11(10)24/h2-5,10-11,13,15-17,19-20,22,25-28H,6-8H2,1H3,(H,29,30)/t10-,11+,13-,15-,16-,17+,19-,20-,22+,23-/m0/s1

HIDE SMILES / InChI

Molecular Formula C23H27NO9
Molecular Weight 461.4618
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 10 / 10
E/Z Centers 0
Optical Activity UNSPECIFIED

Morphine-6-glucuronide is a pharmacologically active metabolite of morphine that is being developed by CeNeS Pharmaceuticals as an alternative to morphine for the management of postoperative pain. Compared to morphine, Morphine-6-glucuronide has been reported to have6 and 86 times lower affinity for the human mu and kappa opioid receptors, respectively, and similar affinity for the delta opioid receptor. Morphine-6-glucuronide is was studied in phase III clinical trials for postoperative pain management. Unfortunately, Morphine-6-glucuronide failed to demonstrate superior safety compared to Morphine and further development was discontinued. Morphine-6-glucuronide accumulates after administration of morphine to patients with renal insufficiency, and analgesia can be obtained with lower doses of morphine compared to patients with normal renal function. More importantly, the dose should be reduced to avoid serious side-effects, although the simulations in this review did not account for side-effects.

Approval Year

PubMed

PubMed

TitleDatePubMed
Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase.
2001 Aug
Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling.
2001 Dec
Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats--pharmacokinetic/pharmacodynamic modelling.
2001 Dec
Hydrophobic forms of morphine-6-glucosides.
2001 Jun 4
Mu opioid receptor efficacy and potency of morphine-6-glucuronide in neonatal guinea pig brainstem membranes: comparison with transfected CHO cells.
2001 Mar 15
Simultaneous expression of guinea pig UDP-glucuronosyltransferase 2B21 and 2B22 in COS-7 cells enhances UDP-glucuronosyltransferase 2B21-catalyzed morphine-6-glucuronide formation.
2001 Nov
Morphine-6beta-glucuronide and morphine-3-glucuronide, opioid receptor agonists with different potencies.
2001 Nov 1
Ethnicity influences morphine pharmacokinetics and pharmacodynamics.
2001 Oct
The role of the hydrophilic Asn230 residue of the mu-opioid receptor in the potency of various opioid agonists.
2001 Oct
Arterial and venous pharmacokinetics of intravenous heroin in subjects who are addicted to narcotics.
2001 Sep
Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids.
2002 Apr
The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide.
2002 Apr
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.
2002 Apr
Verapamil decreases glucuronidase activity in the gut.
2002 Apr 15
Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy.
2002 Aug
The influence of inhibition of probenecid sensitive transporters on the central nervous system (CNS) uptake and the antinociceptive activity of morphine-6-glucuronide in rats.
2002 Aug 30
Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine.
2002 Dec
Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment.
2002 Feb
Increased plasma morphine metabolites in terminally ill cancer patients with delirium: an intra-individual comparison.
2002 Feb
A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer-related breathlessness.
2002 Jan
The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine.
2002 Jan
An automatic 96-well solid phase extraction and liquid chromatography-tandem mass spectrometry method for the analysis of morphine, morphine-3-glucuronide and morphine-6-glucuronide in human plasma.
2002 Jan 1
Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine.
2002 Mar
Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.
2002 May
Contribution of morphine-6-glucuronide to antinociception following intravenous administration of morphine to healthy volunteers.
2002 May
Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy.
2003 Apr
Rapid and simple method to determine morphine and its metabolites in rat plasma by liquid chromatography-mass spectrometry.
2003 Apr 25
Gateways to clinical trials.
2003 Dec
Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients.
2003 Dec
The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment.
2003 Dec
Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.
2003 Dec
Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice.
2003 Dec
Relationships among morphine metabolism, pain and side effects during long-term treatment: an update.
2003 Jan
[Development of opioid tolerance -- molecular mechanisms and clinical consequences].
2003 Jan
Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: a prospective survey in 300 adult cancer patients.
2003 Jul
Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain.
2003 Mar
Gateways to clinical trials.
2003 May
Encapsulation of an intrathecal catheter.
2003 May
Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants.
2003 May
Opioid plasma concentration during switching from morphine to methadone: preliminary data.
2003 May
Peripheral opioid analgesia in experimental human pain models.
2003 May
High levels of morphine-6-glucuronide in street heroin addicts.
2003 Nov
Opiate recidivism in a drug-treatment program: comparison of hair and urine data.
2003 Oct
Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts.
2003 Oct
Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits.
2003 Oct 20
Determination of morphine and morphine glucuronides in human plasma by 96-well plate solid-phase extraction and liquid chromatography-electrospray ionization mass spectrometry.
2003 Oct 25
Different distribution of morphine and morphine-6 beta-glucuronide after intracerebroventricular injection in rats.
2003 Sep
Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children.
2004 Feb
Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences.
2004 Jan
Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys.
2004 Mar
Patents
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:59:18 GMT 2025
Edited
by admin
on Wed Apr 02 09:59:18 GMT 2025
Record UNII
64Y9KYM60R
Record Status Validated (UNII)
Record Version
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Name Type Language
MORPHINE GLUCURONIDE
INN  
INN  
Preferred Name English
MORPHINE-6-GLUCURONIDE
Common Name English
MORPHINE 6-GLUCURONIDE
Common Name English
MORPHINE 6-.BETA.-D-GLUCURONIDE
Common Name English
.BETA.-D-GLUCOPYRANOSIDURONIC ACID, (5.ALPHA.,6.ALPHA.)-7,8-DIDEHYDRO-4,5-EPOXY-3-HYDROXY-17-METHYLMORPHINAN-6-YL
Systematic Name English
morphine glucuronide [INN]
Common Name English
MORPHINE GLUCURONIDE, (-)-
Common Name English
Code System Code Type Description
SMS_ID
100000143116
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
EVMPD
SUB118806
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
NCI_THESAURUS
C166899
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
DRUG BANK
DB06409
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
FDA UNII
64Y9KYM60R
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
PUBCHEM
5360621
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
ChEMBL
CHEMBL611421
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
WIKIPEDIA
MORPHINE-6-GLUCURONIDE
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
EPA CompTox
DTXSID40174158
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
CAS
20290-10-2
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
INN
8377
Created by admin on Wed Apr 02 09:59:18 GMT 2025 , Edited by admin on Wed Apr 02 09:59:18 GMT 2025
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
BINDER->LIGAND
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
SOLVATE->ANHYDROUS
TARGET -> AGONIST
Ratio to morphine 2.3
EC50
TARGET -> AGONIST
Ki
Related Record Type Details
PARENT -> METABOLITE ACTIVE
Approximately 10% of morphine is metabolized to M6G.
MAJOR
Related Record Type Details
ACTIVE MOIETY
In human studies, analgesia potency ratios of M6G, On a weight-for-weight basis, vary from 2– 5 times that of morphine to 1–2 times less than that of morphine. Overall the literature provides significant support for the view that M6G has analgesic efficacy but has a superior side effect profile compared with morphine in man.
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC