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
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
| 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
| Title | Date | PubMed |
|---|---|---|
| Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys. | 2004-03 |
|
| Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. | 2004-02 |
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| Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences. | 2004-01 |
|
| Gateways to clinical trials. | 2003-12 |
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| Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients. | 2003-12 |
|
| The oral-to-intravenous equianalgesic ratio of morphine based on plasma concentrations of morphine and metabolites in advanced cancer patients receiving chronic morphine treatment. | 2003-12 |
|
| Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients. | 2003-12 |
|
| Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice. | 2003-12 |
|
| Repeated exposures to heroin and/or cadmium alter the rate of formation of morphine glucuronides in the rat. | 2003-11 |
|
| Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism. | 2003-11 |
|
| High levels of morphine-6-glucuronide in street heroin addicts. | 2003-11 |
|
| Determination of morphine and morphine glucuronides in human plasma by 96-well plate solid-phase extraction and liquid chromatography-electrospray ionization mass spectrometry. | 2003-10-25 |
|
| Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits. | 2003-10-20 |
|
| Opiate recidivism in a drug-treatment program: comparison of hair and urine data. | 2003-10 |
|
| Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts. | 2003-10 |
|
| Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers. | 2003-10 |
|
| Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium. | 2003-09-05 |
|
| Different distribution of morphine and morphine-6 beta-glucuronide after intracerebroventricular injection in rats. | 2003-09 |
|
| Evidence for an active transport of morphine-6-beta-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier. | 2003-09 |
|
| Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7. | 2003-09 |
|
| Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome. | 2003-08 |
|
| The pharmacokinetics of the interstitial space in humans. | 2003-07-30 |
|
| Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: a prospective survey in 300 adult cancer patients. | 2003-07 |
|
| A novel metabolic pathway of morphine: formation of morphine glucosides in cancer patients. | 2003-06 |
|
| A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. | 2003-06 |
|
| Gateways to clinical trials. | 2003-05 |
|
| Encapsulation of an intrathecal catheter. | 2003-05 |
|
| Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants. | 2003-05 |
|
| Opioid plasma concentration during switching from morphine to methadone: preliminary data. | 2003-05 |
|
| Peripheral opioid analgesia in experimental human pain models. | 2003-05 |
|
| Rapid and simple method to determine morphine and its metabolites in rat plasma by liquid chromatography-mass spectrometry. | 2003-04-25 |
|
| Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the mu-opioid receptor locus (OPRM1). | 2003-04-01 |
|
| Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy. | 2003-04 |
|
| Structure-activity relationships of some opiate glycosides. | 2003-03-24 |
|
| 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. | 2003-03 |
|
| Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. | 2003-01 |
|
| Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. | 2003-01 |
|
| [Development of opioid tolerance -- molecular mechanisms and clinical consequences]. | 2003-01 |
|
| 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. | 2002-12 |
|
| Unwanted effects of morphine-6-glucoronide and morphine. | 2002-12 |
|
| Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. | 2002-12 |
|
| Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity. | 2002-11 |
|
| Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein. | 2002-10 |
|
| 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. | 2002-08-30 |
|
| Pharmacokinetic modeling to predict morphine and morphine-6-glucuronide plasma concentrations in healthy young volunteers. | 2002-08 |
|
| Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. | 2002-08 |
|
| Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone. | 2002-05 |
|
| Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids. | 2002-04 |
|
| Ultrafast liquid chromatography/tandem mass spectrometry bioanalysis of polar analytes using packed silica columns. | 2002 |
|
| Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling. | 2001-12 |
Patents
| Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 09:59:18 GMT 2025
by
admin
on
Wed Apr 02 09:59:18 GMT 2025
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| Record UNII |
64Y9KYM60R
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| Record Status |
Validated (UNII)
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100000143116
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SUB118806
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CHEMBL611421
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MORPHINE-6-GLUCURONIDE
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8377
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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SALT/SOLVATE -> PARENT |
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BINDER->LIGAND |
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> SUBSTRATE |
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SOLVATE->ANHYDROUS |
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TARGET -> AGONIST |
Ratio to morphine 2.3
EC50
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TARGET -> AGONIST |
Ki
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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PARENT -> METABOLITE ACTIVE |
Approximately 10% of morphine is
metabolized to M6G.
MAJOR
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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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.
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Biological Half-life | PHARMACOKINETIC |
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