Population pharmacokinetics of 3,4-methylenedioxymethamphetamine and main metabolites in rats

Toxicological Sciences

Volumn 114, Issue 1, 2009, Pages 38-47

  Hirt, Déborah ^a,b,c   Fonsart, Julien ^a,b,c   Menet, Marie Claude ^a   Debray, Marcel ^a,b,c   Noble, Florence ^a,b,c   Declèves, Xavier ^a,b,c   Scherrmann, Jean Michel ^a,b,c  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b CNRS   (France)

^c INSERM   (France)

Author keywords

HMA; HMMA; MDA; MDMA; Population pharmacokinetics; SD rats

Indexed keywords

3 O METHYL ALPHA METHYLDOPAMINE; 3,4 METHYLENEDIOXYAMPHETAMINE; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4 HYDROXY 3 METHOXYMETAMPHETAMINE; AMPHETAMINE DERIVATIVE; RECREATIONAL DRUG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BODY WEIGHT; COMPARTMENT MODEL; CONTROLLED STUDY; DISTRIBUTION VOLUME; FEMALE; GENDER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; NONHUMAN; NONPARAMETRIC TEST; RANK SUM TEST; RAT; TOXICOKINETICS;

RATTUS;

EID: 77951523520     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfp300     Document Type: Article

References (35)

1. Bai, F., Lau, S.S., and Monks, T.J. (1999). Glutathione and N-acetylcysteine conjugates of alpha-methyldopamine produce serotonergic neurotoxicity: possible role in methylenedioxyamphetamine-mediated neurotoxicity. Chem. Res. Toxicol. 12, 1150-1157.
2. Banks, M.L., Sprague, J.E., Kisor, D.F., Czoty, P.W., Nichols, D.E., and Nader, M.A. (2007). Ambient temperature effects on 3,4-methylenedioxy-methamphetamine-induced thermodysregulation and pharmacokinetics in male monkeys. Drug Metab. Dispos. 35, 1840-1845.
3. Cadet, J.L., Ladenheim, B., Baum, I., Carlson, E., and Epstein, C. (1994). CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA). Brain Res. 655, 259-262.
4. Cho, A.K., Hiramatsu, M., Distefano, E.W., Chang, A.S., and Jenden, D.J. (1990). Stereochemical differences in the metabolism of 3,4-methylenediox-ymethamphetamine in vivo and in vitro: a pharmacokinetic analysis. Drug Metab. Dispos. 18, 686-691.
5. Chu, T., Kumagai, Y., DiStefano, E.W., and Cho, A.K. (1996). Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion. Biochem. Pharmacol. 51, 789-796.
6. Cregg, M.T., and Tracey, J.A. (1993). Ecstasy abuse in Ireland. Ir. Med. J. 86, 118-120.
7. de la Torre, R., and Farre, M. (2004). Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Trends Pharmacol. Sci. 25, 505-508.
8. de la Torre, R., Farre, M., Roset, P.N., Lopez, C.H., Mas, M., Ortuno, J., Menoyo, E., Pizarro, N., Segura, J., and Cami, J. (2000). Pharmacology of MDMA in humans. Ann. N.Y. Acad. Sci. 914, 225-237.
9. Fonsart, J., Menet, M.C., Debray, M., Hirt, D., Noble, F., Scherrmann, J.M., and Decleves, X. (2009). Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA). Toxicol. Appl. Pharmacol. 241, 339-347.
10. Fonsart, J., Menet, M.C., Decleves, X., Galons, H., Crete, D., Debray, M., Scherrmann, J.M., and Noble, F. (2008). Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methyl-enedioxymethamphetamine (MDMA, ecstasy). Toxicol. Appl. Pharmacol. 230, 117-125.
11. Green, A.R., Mechan, A.O., Elliott, J.M., O'Shea, E., and Colado, M.I. (2003). The pharmacology and clinical pharmacology of 3,4-methylene-dioxymethamphetamine (MDMA, "ecstasy"). Pharmacol. Rev. 55, 463-508.
12. Hiramatsu, M., Kumagai, Y., Unger, S.E., and Cho, A.K. (1990). Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphet-amine and a quinone identified as its glutathione adduct. J. Pharmacol. Exp. Ther. 254, 521-527.
13. Johnson, M., Mitros, K., Stone, D.M., Zobrist, R., Hanson, G.R., and Gibb, J.W. (1992). Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 261, 586-591.
14. Jones, D.C., Duvauchelle, C., Ikegami, A., Olsen, C.M., Lau, S.S., de la Torre, R., and Monks, T.J. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J. Pharmacol. Exp. Ther. 313, 422-431.
15. Koenig, J., Lazarus, C., Jeltsch, H., Ben Hamida, S., Riegert, C., Kelche, C., Jones, B.C., and Cassel, J.C. (2005). MDMA (ecstasy) effects in pubescent rats: males are more sensitive than females. Pharmacol. Biochem. Behav. 81, 635-644.
16. Kolbrich, E.A., Goodwin, R.S., Gorelick, D.A., Hayes, R.J., Stein, E.A., and Huestis, M.A. (2008). Plasma pharmacokinetics of 3,4-methylenedioxyme-thamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30, 320-332.
17. Lim, H.K., and Foltz, R.L. (1988). In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector. Chem. Res. Toxicol. 1, 370-378.
18. Lim, H.K., and Foltz, R.L. (1991a). In vivo formation of aromatic hydroxylated metabolites of 3,4-(methylenedioxy)methamphetamine in the rat: identification by ion trap tandem mass spectrometric (MS/MS and MS/MS/MS) techniques. Biol. Mass Spectrom. 20, 677-686.
19. Lim, H.K., and Foltz, R.L. (1991b). Ion trap tandem mass spectrometric evidence for the metabolism of 3,4-(methylenedioxy)methamphetamine to the potent neurotoxins 2,4,5-trihydroxymethamphetamine and 2,4,5-trihydroxyamphetamine. Chem. Res. Toxicol. 4, 626-632.
20. Lofgren, S., Hagbjork, A.L., Ekman, S., Fransson-Steen, R., and Terelius, Y. (2004). Metabolism of human cytochrome P450 marker substrates in mouse: a strain and gender comparison. Xenobiotica 34, 811-834.
21. McKenna, C. (2002). Ecstasy is low in league table of major causes of deaths. BMJ 325, 296.
22. Mechan, A., Yuan, J., Hatzidimitriou, G., Irvine, R.J., McCann, U.D., and Ricaurte, G.A. (2006). Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel monkeys: relationship to lasting effects on brain serotonin neurons. Neuropsychopharmacology 31, 339-350.
23. Meibohm, B., Beierle, I., and Derendorf, H. (2002). How important are gender differences in pharmacokinetics? Clin. Pharmacokinet. 41, 329-342.
24. Miller, D.B., and O'Callaghan, J.P. (1995). The role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. Mol. Neurobiol. 11, 177-192.
25. Mueller, M., Peters, F.T., Maurer, H.H., McCann, U.D., and Ricaurte, G.A. (2008). Nonlinear pharmacokinetics of (+/-)3,4-methylenedioxymetham-phetamine (MDMA, "Ecstasy") and its major metabolites in squirrel monkeys at plasma concentrations of MDMA that develop after typical psychoactive doses. J. Pharmacol. Exp. Ther. 327, 38-44.
26. Mueller, M.A., Yuan, J., Neudorffer, A., Peters, F., Maurer, H., McCann, U., Felim, A.F., Largeron, M., and Ricaurte, G.A. (2009). Further studies on the role of metabolites in MDMA-induced serotonergic neurotoxicity. Drug Metab. Dispos. 37, 2079-2086.
27. Nichols, D.E. (1986). Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J. Psychoactive Drugs 18, 305-313.
28. Parke, J., Holford, N.H., and Charles, B.G. (1999). A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput. Methods Programs Biomed. 59, 19-29.
29. R. The R Foundation or University of Vienna, Vienna, Austria.
30. Schifano, F., Oyefeso, A., Corkery, J., Cobain, K., Jambert-Gray, R., Martinotti, G., and Ghodse, A.H. (2003). Death rates from ecstasy (MDMA, MDA) and polydrug use in England and Wales 1996-2002. Hum. Psychopharmacol. 18, 519-524.
31. Schmidt, C.J., and Taylor, V.L. (1988). Direct central effects of acute methylenedioxymethamphetamine on serotonergic neurons. Eur. J. Pharmacol. 156, 121-131.
32. Shah, V.P., Midha, K.K., Findlay, J.W., Hill, H.M., Hulse, J.D., McGilveray, I.J., McKay, G., Miller, K.J., Patnaik, R.N., Powell, M.L., et al. (2000). Bioanalytical method validation-a revisit with a decade of progress. Pharm. Res. 17, 1551-1557.
33. Thrivikraman, K.V., Huot, R.L., and Plotsky, P.M. (2002). Jugular vein catheterization for repeated blood sampling in the unrestrained conscious rat. Brain Res Brain Res Protoc. 10, 84-94.
34. Tucker, G.T., Lennard, M.S., Ellis, S.W., Woods, H.F., Cho, A.K., Lin, L.Y., Hiratsuka, A., Schmitz, D.A., and Chu, T.Y. (1994). The demethylenation of methylenedioxymethamphetamine ("ecstasy") by debrisoquine hydroxylase (CYP2D6). Biochem. Pharmacol. 47, 1151-1156.
35. Zhao, Z.Y., Castagnoli, N., Jr., Ricaurte, G.A., Steele, T., and Martello, M. (1992). Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)-phenyl] propane [(methylenedioxy)methamphetamine]. Chem. Res. Toxicol. 5, 89-94.