MORPHINE-6-GLUCURONIDE

Investigational

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25861720 | https://www.ncbi.nlm.nih.gov/pubmed/17869146 | https://www.ncbi.nlm.nih.gov/pubmed/18600584

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.

Originator

Approval Year

PubMed

Title	Date	PubMed
Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase.	2001 Aug	11580103
Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling.	2001 Dec	12160091
Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats--pharmacokinetic/pharmacodynamic modelling.	2001 Dec	11739257
Hydrophobic forms of morphine-6-glucosides.	2001 Jun 4	11378376
Mu opioid receptor efficacy and potency of morphine-6-glucuronide in neonatal guinea pig brainstem membranes: comparison with transfected CHO cells.	2001 Mar 15	11397539
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	11641432
Morphine-6beta-glucuronide and morphine-3-glucuronide, opioid receptor agonists with different potencies.	2001 Nov 1	11705461
Ethnicity influences morphine pharmacokinetics and pharmacodynamics.	2001 Oct	11673751
The role of the hydrophilic Asn230 residue of the mu-opioid receptor in the potency of various opioid agonists.	2001 Oct	11588103
Arterial and venous pharmacokinetics of intravenous heroin in subjects who are addicted to narcotics.	2001 Sep	11557911
Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids.	2002 Apr	12061977
The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide.	2002 Apr	11966664
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.	2002 Apr	11964599
Verapamil decreases glucuronidase activity in the gut.	2002 Apr 15	11996900
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	12185559
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	12165398
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	12492606
Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment.	2002 Feb	11844638
Increased plasma morphine metabolites in terminally ill cancer patients with delirium: an intra-individual comparison.	2002 Feb	11844630
A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer-related breathlessness.	2002 Jan	11779662
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	11773859
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	11682220
Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine.	2002 Mar	11969141
Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.	2002 May	12084520
Contribution of morphine-6-glucuronide to antinociception following intravenous administration of morphine to healthy volunteers.	2002 May	12017351
Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy.	2003 Apr	12694145
Rapid and simple method to determine morphine and its metabolites in rat plasma by liquid chromatography-mass spectrometry.	2003 Apr 25	12650748
Gateways to clinical trials.	2003 Dec	14735233
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	14694919
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	14694918
Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.	2003 Dec	14659513
Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice.	2003 Dec	14633759
Relationships among morphine metabolism, pain and side effects during long-term treatment: an update.	2003 Jan	12565191
[Development of opioid tolerance -- molecular mechanisms and clinical consequences].	2003 Jan	12522725
Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: a prospective survey in 300 adult cancer patients.	2003 Jul	12803591
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	12701850
Gateways to clinical trials.	2003 May	12808477
Encapsulation of an intrathecal catheter.	2003 May	12749977
Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants.	2003 May	12697593
Opioid plasma concentration during switching from morphine to methadone: preliminary data.	2003 May	12690541
Peripheral opioid analgesia in experimental human pain models.	2003 May	12690049
High levels of morphine-6-glucuronide in street heroin addicts.	2003 Nov	12774191
Opiate recidivism in a drug-treatment program: comparison of hair and urine data.	2003 Oct	14606994
Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts.	2003 Oct	14534521
Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits.	2003 Oct 20	14522119
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	14552820
Different distribution of morphine and morphine-6 beta-glucuronide after intracerebroventricular injection in rats.	2003 Sep	12967951
Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children.	2004 Feb	14722170
Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences.	2004 Jan	14695733
Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys.	2004 Mar	14634035

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

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