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 |
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Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase. | 2001 Aug |
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Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling. | 2001 Dec |
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Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats--pharmacokinetic/pharmacodynamic modelling. | 2001 Dec |
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Hydrophobic forms of morphine-6-glucosides. | 2001 Jun 4 |
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Mu opioid receptor efficacy and potency of morphine-6-glucuronide in neonatal guinea pig brainstem membranes: comparison with transfected CHO cells. | 2001 Mar 15 |
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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 |
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Morphine-6beta-glucuronide and morphine-3-glucuronide, opioid receptor agonists with different potencies. | 2001 Nov 1 |
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Ethnicity influences morphine pharmacokinetics and pharmacodynamics. | 2001 Oct |
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The role of the hydrophilic Asn230 residue of the mu-opioid receptor in the potency of various opioid agonists. | 2001 Oct |
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Arterial and venous pharmacokinetics of intravenous heroin in subjects who are addicted to narcotics. | 2001 Sep |
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Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids. | 2002 Apr |
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The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide. | 2002 Apr |
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Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. | 2002 Apr |
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Verapamil decreases glucuronidase activity in the gut. | 2002 Apr 15 |
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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 |
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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 |
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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 |
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Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment. | 2002 Feb |
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Increased plasma morphine metabolites in terminally ill cancer patients with delirium: an intra-individual comparison. | 2002 Feb |
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A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer-related breathlessness. | 2002 Jan |
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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 |
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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 |
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Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine. | 2002 Mar |
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Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone. | 2002 May |
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Contribution of morphine-6-glucuronide to antinociception following intravenous administration of morphine to healthy volunteers. | 2002 May |
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Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy. | 2003 Apr |
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Rapid and simple method to determine morphine and its metabolites in rat plasma by liquid chromatography-mass spectrometry. | 2003 Apr 25 |
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Gateways to clinical trials. | 2003 Dec |
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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 Dec |
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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 |
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Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients. | 2003 Dec |
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Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice. | 2003 Dec |
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Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. | 2003 Jan |
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[Development of opioid tolerance -- molecular mechanisms and clinical consequences]. | 2003 Jan |
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Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: a prospective survey in 300 adult cancer patients. | 2003 Jul |
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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 |
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Gateways to clinical trials. | 2003 May |
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Encapsulation of an intrathecal catheter. | 2003 May |
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Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants. | 2003 May |
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Opioid plasma concentration during switching from morphine to methadone: preliminary data. | 2003 May |
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Peripheral opioid analgesia in experimental human pain models. | 2003 May |
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High levels of morphine-6-glucuronide in street heroin addicts. | 2003 Nov |
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Opiate recidivism in a drug-treatment program: comparison of hair and urine data. | 2003 Oct |
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Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts. | 2003 Oct |
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Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits. | 2003 Oct 20 |
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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 |
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Different distribution of morphine and morphine-6 beta-glucuronide after intracerebroventricular injection in rats. | 2003 Sep |
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Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. | 2004 Feb |
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Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences. | 2004 Jan |
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Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys. | 2004 Mar |
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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C166899
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DB06409
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5360621
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CHEMBL611421
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MORPHINE-6-GLUCURONIDE
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DTXSID40174158
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20290-10-2
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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 |
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Biological Half-life | PHARMACOKINETIC |
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