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
Morphine-6-glucuronide: an analgesic of the future?	2001	11510626
Simultaneous determination of morphine and its glucuronides in rat hair and rat plasma by reversed-phase liquid chromatography with electrospray ionization mass spectrometry.	2001 Aug	11534602
mu Opioid receptor-mediated G-protein activation by heroin metabolites: evidence for greater efficacy of 6-monoacetylmorphine compared with morphine.	2001 Aug 15	11448454
Pharmacokinetics of morphine and its glucuronidated metabolites in burn injuries.	2001 Dec	11793627
Pharmacokinetics of morphine 3-esters after oral administration in rabbits.	2001 Jun	11446167
Arterial and venous pharmacokinetics of intravenous heroin in subjects who are addicted to narcotics.	2001 Sep	11557911
[Issues in cancer pain management].	2001 Sep	11554059
LC determination of morphine and morphine glucuronides in human plasma by coulometric and UV detection.	2001 Sep	11470195
Wheel running attenuates the antinociceptive properties of morphine and its metabolite, morphine-6-glucuronide, in rats.	2001 Sep 1-15	11564474
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
Quantitative gas chromatographic/mass spectrometric analysis of morphine glucuronides in human plasma by negative ion chemical ionization mass spectrometry.	2002 Apr	11948846
Intranasal delivery of morphine.	2002 Apr	11907197
Verapamil decreases glucuronidase activity in the gut.	2002 Apr 15	11996900
Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation.	2002 Feb	11911556
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
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
A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer-related breathlessness.	2002 Jan	11779662
Morphine in cancer pain management: a practical guide.	2002 Jan	11777184
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
A polymorphism (A118G) in the mu-opioid receptor gene affects the response to morphine-6-glucuronide in humans.	2002 Jan	11773858
Colostrum morphine concentrations during postcesarean intravenous patient-controlled analgesia.	2002 Jan	11772825
Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine.	2002 Mar	11969141
Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.	2002 Mar	11964135
Contribution of morphine-6-glucuronide to antinociception following intravenous administration of morphine to healthy volunteers.	2002 May	12017351
Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the mu-opioid receptor locus (OPRM1).	2003 Apr 1	12627468
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
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
Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers.	2003 Jan	12545149
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 pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.	2003 Jun	12811366
Gateways to clinical trials.	2003 May	12808477
Encapsulation of an intrathecal catheter.	2003 May	12749977
Opioid plasma concentration during switching from morphine to methadone: preliminary data.	2003 May	12690541
Repeated exposures to heroin and/or cadmium alter the rate of formation of morphine glucuronides in the rat.	2003 Nov	12975487
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
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