Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C23H27NO9.2H2O |
| Molecular Weight | 497.4923 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 10 / 10 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.[H][C@@]12OC3=C4C(C[C@@]5([H])N(C)CC[C@@]14[C@@]5([H])C=C[C@@H]2O[C@@H]6O[C@@H]([C@@H](O)[C@H](O)[C@H]6O)C(O)=O)=CC=C3O
InChI
InChIKey=NRBQUVXMCUQJPZ-WFLHAITMSA-N
InChI=1S/C23H27NO9.2H2O/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);2*1H2/t10-,11+,13-,15-,16-,17+,19-,20-,22+,23-;;/m0../s1
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 |
|---|---|---|
| Identifying potential binding modes and explaining partitioning behavior using flexible alignments and multidimensional scaling. | 2001 Dec |
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| Ultrafast liquid chromatography/tandem mass spectrometry bioanalysis of polar analytes using packed silica columns. | 2002 |
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| Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids. | 2002 Apr |
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| Pharmacokinetic modeling to predict morphine and morphine-6-glucuronide plasma concentrations in healthy young volunteers. | 2002 Aug |
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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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| Unwanted effects of morphine-6-glucoronide and morphine. | 2002 Dec |
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| Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. | 2002 Dec |
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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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| Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity. | 2002 Nov |
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| Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein. | 2002 Oct |
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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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| Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the mu-opioid receptor locus (OPRM1). | 2003 Apr 1 |
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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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| Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome. | 2003 Aug |
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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 |
|
| 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 |
|
| Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. | 2003 Jan |
|
| Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. | 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 |
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| The pharmacokinetics of the interstitial space in humans. | 2003 Jul 30 |
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| A novel metabolic pathway of morphine: formation of morphine glucosides in cancer patients. | 2003 Jun |
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| A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. | 2003 Jun |
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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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| Structure-activity relationships of some opiate glycosides. | 2003 Mar 24 |
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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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| Repeated exposures to heroin and/or cadmium alter the rate of formation of morphine glucuronides in the rat. | 2003 Nov |
|
| Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism. | 2003 Nov |
|
| 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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| Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers. | 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 |
|
| Different distribution of morphine and morphine-6 beta-glucuronide after intracerebroventricular injection in rats. | 2003 Sep |
|
| Evidence for an active transport of morphine-6-beta-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier. | 2003 Sep |
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| Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7. | 2003 Sep |
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| Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium. | 2003 Sep 5 |
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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 |
|
| Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys. | 2004 Mar |
Patents
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ARKJBVK150
Created by
admin on Fri Dec 15 15:36:46 GMT 2023 , Edited by admin on Fri Dec 15 15:36:46 GMT 2023
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71308353
Created by
admin on Fri Dec 15 15:36:46 GMT 2023 , Edited by admin on Fri Dec 15 15:36:46 GMT 2023
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PRIMARY |
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
