Morphine-6 3-glucuronide

Lotsch J, Zimmermann M, Darimont J, et al Does the Al 18G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity Anesthesiology 97 814-819, 2002... 

Skarke C, Darimont J, Schmidt H, et al Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. Clin Pharmacol Ther 73 107—121, 2003... 

Cross A, Asher L, Seguin M, Yuan L, Kelly N, Hammack C (1995) The importance of a hpopoly-sacchaiide-initiated, cytokine-mediated host defense mechanism in mice against extraintesti-nally invasive escheiichia coh. J Clin Invest 96(2) 676-686 Dahan A, van Dorp E, Smith T, Yassen A (2008) Morphine-6-glucuronide (M6G) for postoperative pain relief. Eur J Pain 12(4) 403-411... 

Avdeef, A. Barrett, D. A. Shaw, P. N. Knaggs, R. D. Davis, S. S.,Octanol-, chloroform-, and PGDP-water partitioning of morphine-6-glucuronide and other related opiates, J. Med. Chem. 39, 4377 1381 (1996). 

Carrupt, P.-A. Testa, B. Bechalany, A. El Tayar, N. Descas, P. Perrissoud, D., Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpectedly high lipophilicity, J. Med. Chem. 34, 1272-1275 (1991). 

Per-O-acylated glycosyl iodides are stable at room temperature and can be purified on a silica gel column and stored at 0 °C. Stachulski and coworkers [202] synthesized methyl 2,3,4-tri-O-pivaloyl-glucopyranuroate iodide, which is a stable solid at 20 °C and can be stored for months at room temperature or for more than a year at 0 °C. The X-ray crystal structure of this compound, the first one of this class, shows a typical chair structure. Importantly, such a disarmed and stable iodide can be coupled with primary and secondary steroidal alcohols using I2 as a promoter, as demonstrated by the synthesis of morphine-6-glucuronide, an analgesic [202], The glycosyl donor ability... 

F. Stain-Texier, P. Sandouk, J. M. Scherrmann, Intestinal Absorption and Stability of Morphine 6-Glucuronide in Different Physiological Compartments of the Rat , Drug Metab. Dispos. 1998, 26, 383 - 387. 

Rotshteyn Y, Weingarten B. 1996. A highly sensitive assay for the simultaneous determination of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in human plasma by high-performance liquid chromatography with electrochemical and fluorescence detection. Ther Drug Monit 18(2) 179-188. 

Dahan A, van Dorp E, Smith T, Yassen A. (2008) Morphine-6-glucuronide (M6G) for postoperative pain relief. Eur J Pain 12 403 11. 

Kilpatrick GJ, Smith TW. (2005) Morphine-6-glucuronide Actions and mechanisms. Med Res Rev 25 521-544. For further information PAION. Press release 3 November 2008. Available at http //www.paion.com/. 

Codeine phosphate is still used for diarrhea predominantly based on hypermotility but the longer-acting loperamide is more convenient and has less central nervous system effects. Codeine has an exceptionally low affinity for opioid receptors and its effects are due to the fact that it is converted for approximately 10% to morphine. The active metabolite of morphine, morphine-6-glucuronide, may also accumulate during repeated administration of codeine to patients with impaired renal function. 

Kilpatrick GJ, Smith TW. Morphine-6-glucuronide actions and mechanisms. Med Res Rev 2005 25(5) 521-44. 

The majority of their metabolites are inactive with a few notable exceptions, such as morphine-6-glucuronide, which produces an analgesic effect normeperidine and norpropoxyphene, which produce excitatory but not analgesic effects and 6-(3-naltexol, which is less active than naltrexone as an antagonist but prolongs the action of naltrexone. Excretion of the metabolites requires adequate renal function, since excretion by routes other than the urine are of minor importance. 

The clearance of morphine and its active metabolite, morphine-6-glucuronide depends on adequate renal function. The elderly are particularly susceptible to accumulation of the drugs, hence respiratory depression and sedation. Morphine, like all opioids, passes through the placenta rapidly and has been associated with prolongation of labor in pregnant women and respiratory depression in the newborn. 

Lotsch, J. and Geisslinger, G. Morphine-6-glucuronide an analgesic of the future , Clin. Pharmacokinet. 2001, 40, 485-499. 

Osborne, R., Joel, S., Trew, D., Slevin, M. Morphine and metabolite behavior after different routes of morphine administration demonstration of the importance of the active metabolite morphine-6-glucuronide, Clin. Pharmacol. Ther. 1990, 47, 12-19. 

Schwarzinger, S., Hartmann, M., Kremminger, P., Muller, N. Hydrophobic forms of morphine-6-glucuronides, Bioorg. Med. Chem. Lett. 2001, 11, 1455-1459. 

Klepstad, P., S. Kaasa, and P.C. Borchgrevink, Start of oral morphine to cancer patients effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine, Eur. J. Clin. Pharmacol., 55(10), 713-719, 2000. 

Lotsch, J., A. Stockmann, G. Kobal, K. Brune, et al., Pharmacokinetics of morphine and its glucu-ronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers, Clin. Pharmacol. Ther., 60(3), 316-325, 1996. 

R. T. Brown, N. E. Carter, K. W. Lumbard, and F. Scheinmann, Synthesis of a morphine-6-glucuronide hapten,, V-(4-aminobutyl)normorphine-6-glucuromde, and related haptens, Tetrahedron. Lett., 36 (1995) 8661-8664. 

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