Nonlinear pharmacokinetics of (±)3,4-methylenedioxymethamphetamine (MDMA) and its pharmacodynamic consequences in the rat

Drug Metabolism and Disposition

Volumn 42, Issue 1, 2014, Pages 119-125

  Concheiro, Marta ^a   Baumann, Michael H ^a   Scheidweiler, Karl B ^a   Rothman, Richard B ^a   Marrone, Gina F ^b   Huestis, Marilyn A ^a  

^a NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3,4 DIHYDROXYMETHAMPHETAMINE; 3,4 METHYLENEDIOXYAMPHETAMINE; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4 HYDROXY 3 METHOXYMETHAMPHETAMINE; AMPHETAMINE DERIVATIVE; DRUG METABOLITE; SEROTONIN; UNCLASSIFIED DRUG; 4-HYDROXY-3-METHOXYMETHAMPHETAMINE; DRUG DERIVATIVE; METHAMPHETAMINE;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; CORE TEMPERATURE; CORRELATION ANALYSIS; DISEASE SEVERITY; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; HYPERTHERMIA; JUGULAR VEIN; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; RAT; SEROTONIN SYNDROME; TANDEM MASS SPECTROMETRY; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; METABOLISM; SPRAGUE DAWLEY RAT;

3,4-METHYLENEDIOXYAMPHETAMINE; ANIMALS; AREA UNDER CURVE; MALE; METHAMPHETAMINE; N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; RATS; RATS, SPRAGUE-DAWLEY; SEROTONIN;

EID: 84890620696     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.113.053678     Document Type: Article

References (45)

1. Baumann MH, Clark RD, Franken FH, Rutter JJ, and Rothman RB (2008) Tolerance to 3, 4-methylenedioxymethamphetamine in rats exposed to single high-dose binges. Neuroscience 152:773-784.
2. Baumann MH and Rothman RB (2009) Neural and cardiac toxicities associated with 3, 4-meth-ylenedioxymethamphetamine (MDMA). Int Rev Neurobiol 88:257-296.
3. Baumann MH, Wang X, and Rothman RB (2007) 3, 4- Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology (Berl) 189: 407-424. (Pubitemid 44791212)
4. Baumann MH, Zolkowska D, Kim I, Scheidweiler KB, Rothman RB, and Huestis MA (2009) Effects of dose and route of administration on pharmacokinetics of (+ or-)-3, 4-methyl-enedioxymethamphetamine in the rat. Drug Metab Dispos 37:2163-2170.
5. Brady JF, Di Stefano EW, and Cho AK (1986) Spectral and inhibitory interactions of (+/-)-3, 4-methylenedioxyamphetamine (MDA) and (+/-)-3, 4-methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes. Life Sci 39:1457-1464. (Pubitemid 16031641)
6. Chu T, Kumagai Y, DiStefano EW, and Cho AK (1996) Disposition of methylenedioxymethamphet-amine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion. Biochem Pharmacol 51:789-796. (Pubitemid 26094447)
7. de la Torre R and Farré M (2004) Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Trends Pharmacol Sci 25:505-508. (Pubitemid 39233561)
8. de la Torre R, Farré M, Ortuño J, Mas M, Brenneisen R, Roset PN, Segura J, and Camí J (2000) Non-linear pharmacokinetics of MDMA ('ecstasy') in humans. Br J Clin Pharmacol 49: 104-109. (Pubitemid 30068287)
9. de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, and Camí J (2004) Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit 26:137-144. (Pubitemid 38501207)
10. Delaforge M, Jaouen M, and Bouille G (1999) Inhibitory metabolite complex formation of methylenedioxymethamphetamine with rat and human cytochrome P450. Particular involvement of CYP 2D. Environ Toxicol Pharmacol 7:153-158. (Pubitemid 29341574)
11. Farré M, de la Torre R, Mathúna BO, Roset PN, Peiró AM, Torrens M, Ortuño J, Pujadas M, and Camí J (2004) Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics. Psychopharmacology (Berl) 173:364-375. (Pubitemid 38703810)
12. Goni-Allo B, O Mathúna B, Segura M, Puerta E, Lasheras B, de la Torre R, and Aguirre N (2008) The relationship between core body temperature and 3, 4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity. Psychopharmacology (Berl) 197:263-278.
13. Green AR, Gabrielsson J, Marsden CA, and Fone KC (2009) MDMA: on the translation from rodent to human dosing. Psychopharmacology (Berl) 204:375-378.
14. Green AR, King MV, Shortall SE, and Fone KCF (2012) Lost in translation: preclinical studies on 3, 4-methylenedioxymethamphetamine provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans. Br J Pharmacol 166: 1523-1536.
15. Heydari A, Yeo KR, Lennard MS, Ellis SW, Tucker GT, and Rostami-Hodjegan A (2004) Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine. Drug Metab Dispos 32:1213-1217. (Pubitemid 39410904)
16. Hirt D, Fonsart J, Menet M-C, Debray M, Noble F, Declèves X, and Scherrmann J-M (2010) Population pharmacokinetics of 3, 4- methylenedioxymethamphetamine and main metabolites in rats. Toxicol Sci 114:38-47.
17. Institute of Laboratory Animal Resources (1996) Guide for the Care and Use of Laboratory Animals, 7th ed. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, Washington, DC.
18. Johanson CE, Kilbey M, Gatchalian K, and Tancer M (2006) Discriminative stimulus effects of 3, 4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo. Drug Alcohol Depend 81:27-36. (Pubitemid 41682476)
19. Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, and Huestis MA (2008a) Physiological and subjective responses to controlled oral 3, 4-methylenedioxymethamphetamine administration. J Clin Psychopharmacol 28:432-440.
20. Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, and Huestis MA (2008b) Plasma pharmacokinetics of 3, 4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther Drug Monit 30:320-332.
21. Lim HK, Zeng S, Chei DM, and Foltz RL (1992) Comparative investigation of disposition of 3, 4-(methylenedioxy)methamphetamine (MDMA) in the rat and the mouse by a capillary gas chromatography-mass spectrometry assay based on perfluorotributylamine-enhanced ammonia positive ion chemical ionization. J Pharm Biomed Anal 10:657-665. (Pubitemid 23009569)
22. Logan BK (2001) Amphetamines: an update on forensic issues. J Anal Toxicol 25:400-404. (Pubitemid 32656294)
23. Mas M, Farré M, de la Torre R, Roset PN, Ortuño J, Segura J, and Camí J (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290:136-145. (Pubitemid 29302313)
24. Maurer HH, Bickeboeller-Friedrich J, Kraemer T, and Peters FT (2000) Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ('Ecstasy'). Toxicol Lett 112-113:133-142. (Pubitemid 30138114)
25. Mechan AO, Esteban B, O'Shea E, Elliott JM, Colado MI, and Green AR (2002) The pharmacology of the acute hyperthermic response that follows administration of 3, 4-methylenediox-ymethamphetamine (MDMA, 'ecstasy') to rats. Br J Pharmacol 135:170-180. (Pubitemid 34102110)
26. Meyer JS, Piper BJ, and Vancollie VE (2008) Development and characterization of a novel animal model of intermittent MDMA ("Ecstasy") exposure during adolescence. Ann N Y Acad Sci 1139:151-163.
27. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, and Doblin R (2011) The safety and efficacy of +/-3, 4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol 25:439-452.
28. Mueller M, Peters F, Maurer H, McCann U, and Ricaurte GA (2008) Non-linear pharmacokinetics of 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.
29. Mueller M, Peters FT, Ricaurte GA, and Maurer HH (2007) Validated liquid chromatographic-electrospray ionization mass spectrometric assay for simultaneous determination of 3, 4-methylenedioxymethamphetamine and its metabolites 3, 4-methylenedioxyamphetamine, 3, 4-dihydroxymethamphetamine, and 4-hydroxy-3-methoxymethamphetamine in squirrel monkey plasma. J Chromatogr B Analyt Technol Biomed Life Sci 855:262-270. (Pubitemid 47212023)
30. Mueller M, Yuan J, Felim A, Neudörffer A, Peters FT, Maurer HH, McCann UD, Largeron M, and Ricaurte GA (2009) Further studies on the role of metabolites in (+/-)-3, 4-methylenedioxymethamphetamine-induced serotonergic neurotoxicity. Drug Metab Dispos 37:2079-2086.
31. Murray M (1997) Drug-mediated inactivation of cytochrome P450. Clin Exp Pharmacol Physiol 24:465-470. (Pubitemid 27273820)
32. Ricaurte GA, Yuan J, and McCann UD (2000) (+/-)3, 4- Methylenedioxymethamphetamine ('Ecstasy')-induced serotonin neurotoxicity: studies in animals. Neuropsychobiology 42:5-10. (Pubitemid 30436310)
33. Rodsiri R, Spicer C, Green AR, Marsden CA, and Fone KC (2011) Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Psychopharmacology (Berl) 213:365-376.
34. Schechter MD (1988) Serotonergic-dopaminergic mediation of 3, 4-methylenedioxymethamphet-amine (MDMA, "ecstasy"). Pharmacol Biochem Behav 31:817-824. (Pubitemid 19274289)
35. Scheidweiler KB, Ladenheim B, Barnes AJ, Cadet JL, and Huestis MA (2011) (±)-3, 4-Meth-ylenedioxymethamphetamine and metabolite disposition in plasma and striatum of wild-type and multidrug resistance protein 1a knock-out mice. J Anal Toxicol 35:470-480.
36. Segura M, Ortuño J, Farré M, McLure JA, Pujadas M, Pizarro N, Llebaria A, Joglar J, Roset PN, and Segura J, et al. (2001) 3, 4-Dihydroxymethamphetamine (HHMA). A major in vivo 3, 4- methylenedioxymethamphetamine (MDMA) metabolite in humans. Chem Res Toxicol 14: 1203-1208. (Pubitemid 32911458)
37. Shima N, Katagi M, Kamata H, Zaitsu K, Kamata T, Nishikawa M, Miki A, Tsuchihashi H, Sakuma T, and Nemoto N (2008) Urinary excretion of the main metabolites of 3, 4-methyl-enedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats. Xenobiotica 38:314-324. (Pubitemid 351264448)
38. Shulgin AT, Nichols DE (1978) Characterization of three new psychotomimetics, in The Psychopharmacology of Hallucinogens (Stillman RC, Willette RE eds) pp 74-83, Pergamon Press, New York.
39. Starr MA, Page ME, and Waterhouse BD (2008) MDMA (3, 4- methylenedioxymethamphetamine)-mediated distortion of somatosensory signal transmission and neurotransmitter efflux in the ventral posterior medial thalamus. J Pharmacol Exp Ther 327:20-31.
40. United Nations (2012) World Drug Report 2012, United Nations Publications, New York.
41. Upreti VV and Eddington ND (2008) Fluoxetine pretreatment effects pharmacokinetics of 3, 4-methylenedioxymethamphetamine (MDMA, ECSTASY) in rat. J Pharm Sci 97:1593-1605.
42. Valtier S, Phelix CF, and Cody JT (2007) Analysis of MDMA and its metabolites in urine and plasma following a neurotoxic dose of MDMA. J Anal Toxicol 31:138-143. (Pubitemid 46641584)
43. Verrico CD, Miller GM, and Madras BK (2007) MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl) 189:489-503. (Pubitemid 44791219)
44. Walubo A and Seger D (1999) Fatal multi-organ failure after suicidal overdose with MDMA, 'ecstasy': case report and review of the literature. Hum Exp Toxicol 18:119-125. (Pubitemid 29087953)
45. Wu D, Otton SV, Inaba T, Kalow W, and Sellers EM (1997) Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol 53:1605-1612. (Pubitemid 27356089)