morphine and morphine-6-glucuronide

morphine has been researched along with morphine-6-glucuronide* in 6 studies

Other Studies

6 other study(ies) available for morphine and morphine-6-glucuronide

ArticleYear
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
    Bioorganic & medicinal chemistry, 2013, Dec-15, Volume: 21, Issue:24

    We have previously found that phenanthrenic opioids, including codeine, modulate morphine glucuronidation in the rat. Here codeine and five of its derivatives were compared in their effects on the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine by rat liver microsomal preparations, and by primary cultures of rat hepatocytes previously incubated for 72 h with either codeine or its derivatives. Acetylcodeine and pivaloylcodeine shared the capability of the parent compound of inhibiting the synthesis of M3G by liver microsomes through a noncompetitive mechanism of action. Their IC50 were 3.25, 2.27, and 4.32 μM, respectively. Dihydrocodeine, acetyldihydrocodeine, and lauroylcodeine were ineffective. In all the experimental circumstances M6G was undetectable in the incubation medium. In primary hepatocyte cultures codeine only inhibited M3G formation, but with a lower efficacy than that observed with microsomes (IC50 20.91 vs 4.32 μM). Preliminary results show that at micromolar concentrations codeine derivatives exhibit a low rate of affinity for μ opiate receptors. In conclusion, acetyl and pivaloyl derivatives of codeine noncompetitively inhibit liver glucuronidation of morphine interacting with microsomes. This study further strengths the notion that phenanthrenic opioids can modulate morphine glucuronidation independently from their effects on μ opiate receptors.

    Topics: Animals; Codeine; Dose-Response Relationship, Drug; Hepatocytes; Kinetics; Male; Microsomes, Liver; Molecular Structure; Morphine Derivatives; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

2013
Synthesis and biological evaluation of analogues of M6G.
    European journal of medicinal chemistry, 2011, Volume: 46, Issue:9

    Synthesis and biological evaluation of new derivatives of Morphine-6-Glucuronide (M6G) are described. M6G is an active metabolite of morphine which displays more analgesia than morphine with a superior side effect profile but with a less efficiently BBB penetration. These phenomena could be explained by the presence of the glucuronide moiety, which confers a higher hydrophilic character compare to morphine. In this context, we have prepared three analogues of M6G possessing a tetrazole, an oxadiazole, and a triazolopyrimidine moiety instead of the carboxylic acid function on position 5 of the sugar. These three analogues showed higher analgesic properties than morphine and M6G even by oral administration.

    Topics: Analgesics, Opioid; Animals; Blood-Brain Barrier; Magnetic Resonance Spectroscopy; Male; Mice; Morphine Derivatives; Spectrometry, Mass, Electrospray Ionization

2011
Design, chemical synthesis, and biological evaluation of thiosaccharide analogues of morphine- and codeine-6-glucuronide.
    Journal of medicinal chemistry, 2004, Nov-04, Volume: 47, Issue:23

    A series of 6-beta-thiosaccharide analogues of morphine-6-glucuronide (M6G) and codeine-6-glucuronide (C6G) were synthesized and evaluated with the objective of preparing an analogue of M6G with improved biological activity. The affinity of the thiosaccharide analogues of M6G and C6G was examined by competitive binding assays at mu, delta, and kappa opioid receptors. The thiosaccharide compounds in the morphine series 5b, 5e, 6a, and 6c showed 1.5-2.4-fold higher affinity for the mu receptor than M6G, but were generally less selective than M6G. The functional activity of the M6G and C6G analogues was examined with the [35S]GTP-gamma-S assay. Compounds 5b and 5e were determined to be full mu agonists, whereas compounds 6a and 6c were partial mu agonists. The in vivo antinociceptive activity of compound 5b was evaluated by the tail flick latency test, giving an ED50 of 2.5 mg/kg.

    Topics: Analgesics, Opioid; Animals; Binding, Competitive; Codeine; Drug Design; Glycosides; Male; Mice; Mice, Inbred ICR; Morphine Derivatives; Radioligand Assay; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Structure-Activity Relationship; Sulfides

2004
Structure-activity relationships of some opiate glycosides.
    Bioorganic & medicinal chemistry letters, 2003, Mar-24, Volume: 13, Issue:6

    A number of analogues of morphine-6-glucuronide 1 have been prepared and evaluated as potential analgesic agents by competitive mu-receptor binding assay and in vivo antinociceptive activity. The analogues show variation in the nature of the carbohydrate residue, the N-substituent, the O(3)-substituent and saturation of the 7,8-double bond compared to 1. In general, only the 6beta-glucoside or beta-glucuronide carbohydrate residues showed potent agonism; other modified carbohydrates were less active or exhibited potential antagonism. Variations in N-substituent led to either reduced agonism (N-H) or potential antagonism [N-allyl, N-(cyclopropyl)methyl]; a polar N-substituent, carboxymethyl, failed to bind. Saturation of the 7,8-double bond led to increased agonism compared to the parent compound in all three examples studied.

    Topics: Animals; Carbohydrate Sequence; Codeine; Glycosides; Mice; Molecular Sequence Data; Morphine Derivatives; Narcotics; Pain Measurement; Reaction Time; Receptors, Opioid, mu; Structure-Activity Relationship

2003
Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates.
    Journal of medicinal chemistry, 1996, Oct-25, Volume: 39, Issue:22

    Topics: Biological Transport; Chemical Phenomena; Chemistry, Physical; Chloroform; Hydrogen-Ion Concentration; Morphine Derivatives; Narcotics; Octanols; Potentiometry; Solutions; Solvents

1996
Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity.
    Journal of medicinal chemistry, 1991, Volume: 34, Issue:4

    Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist. In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug. Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes. Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself. Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extended and folded forms. The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membranes.

    Topics: Calorimetry; Computer Graphics; Indicators and Reagents; Models, Molecular; Molecular Conformation; Morphine Derivatives

1991