MORPHINE-6-GLUCURONIDE

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

[H][C@@]12OC3=C4C(C[C@H]5N(C)CC[C@@]14[C@@]5([H])C=C[C@@H]2O[C@]6([H])O[C@@H]([C@@H](O)[C@H](O)[C@H]6O)C(O)=O)=CC=C3O

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
Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling.	2001 Dec	12160091
Ultrafast liquid chromatography/tandem mass spectrometry bioanalysis of polar analytes using packed silica columns.	2002	12203228
Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids.	2002 Apr	12061977
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.	2002 Apr	11964599
Intranasal delivery of morphine.	2002 Apr	11907197
Pharmacokinetic modeling to predict morphine and morphine-6-glucuronide plasma concentrations in healthy young volunteers.	2002 Aug	12189362
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
Unwanted effects of morphine-6-glucoronide and morphine.	2002 Dec	12479189
Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability.	2002 Dec	12453926
Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation.	2002 Feb	11911556
Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.	2002 Feb 27	11943073
Cold stress alters Mytilus edulis pedal ganglia expression of mu opiate receptor transcripts determined by real-time RT-PCR and morphine levels.	2002 Feb 28	11869805
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
Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein.	2002 Oct	12423235
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
Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome.	2003 Aug	12895198
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
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
The pharmacokinetics of the interstitial space in humans.	2003 Jul 30	12890292
A novel metabolic pathway of morphine: formation of morphine glucosides in cancer patients.	2003 Jun	12814451
A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.	2003 Jun	12811366
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
Structure-activity relationships of some opiate glycosides.	2003 Mar 24	12643945
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
Repeated exposures to heroin and/or cadmium alter the rate of formation of morphine glucuronides in the rat.	2003 Nov	12975487
Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.	2003 Nov	12897995
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
Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers.	2003 Oct	14508308
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
Evidence for an active transport of morphine-6-beta-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier.	2003 Sep	12950465
Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7.	2003 Sep	12920162
Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.	2003 Sep 5	12954379
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 `Sat Dec 16 18:02:28 GMT 2023` Edited by `admin` on `Sat Dec 16 18:02:28 GMT 2023`
Record UNII	64Y9KYM60R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MORPHINE-6-GLUCURONIDE

Common Name

English

MORPHINE 6-GLUCURONIDE

Common Name

English

MORPHINE 6-.BETA.-D-GLUCURONIDE

Common Name

English

MORPHINE GLUCURONIDE

Official 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