Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug–drug interactions

References

• Aguirre N, Ballaz S, Lasheras B, Del Río J. (1998). MDMA (‘Ecstasy’) enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion. Eur J Pharmacol 346:181–188.
   PubMedGoogle Scholar
• Aitchison KJ, Tsapakis EM, Huezo-Diaz P, Kerwin RW, Forsling ML, Wolff K. (2012). Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT. J Psychopharmacol (Oxford) 26:408–418.
   PubMed Web of Science ®Google Scholar
• Al-Dabbagh SG, Idle JR, Smith RL. (1981). Animal modelling of human polymorphic drug oxidation–the metabolism of debrisoquine and phenacetin in rat inbred strains. J Pharm Pharmacol 33:161–164.
   PubMed Web of Science ®Google Scholar
• Antolino-Lobo I, Meulenbelt J, Nijmeijer SM, Scherpenisse P, van den Berg M, van Duursen MB. (2010). Differential roles of phase I and phase II enzymes in 3,4-methylendioxymethamphetamine-induced cytotoxicity. Drug Metab Dispos 38:1105–1112.
   PubMed Web of Science ®Google Scholar
• Antolino-Lobo I, Meulenbelt J, Molendijk J, Nijmeijer SM, Scherpenisse P, van den Berg M, van Duursen MB. (2011a). Induction of glutathione synthesis and conjugation by 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dihydroxymethamphetamine (HHMA) in human and rat liver cells, including the protective role of some antioxidants. Toxicology 289:175–184.
   PubMed Web of Science ®Google Scholar
• Antolino-Lobo I, Meulenbelt J, van den Berg M, van Duursen MB. (2011b). A mechanistic insight into 3,4-methylenedioxymethamphetamine (“ecstasy”)-mediated hepatotoxicity. Vet Q 31:193–205.
   PubMed Web of Science ®Google Scholar
• Arrue A, Ruiz-Ortega JA, Ugedo L, Giralt MT. (2003). Short-term effects of 3,4-methylenedioximethamphetamine on noradrenergic activity in locus coeruleus and hippocampus of the rat. Neurosci Lett 337:123–126.
   PubMedGoogle Scholar
• Bal-Price AK, Hogberg HT, Buzanska L, Coecke S. (2010). Relevance of in vitro neurotoxicity testing for regulatory requirements: challenges to be considered. Neurotoxicol Teratol 32:36–41.
   PubMedGoogle Scholar
• Barbosa DJ, Capela JP, Oliveira JM, Silva R, Ferreira LM, Siopa F, Branco PS, Fernandes E, Duarte JA, de Lourdes Bastos M, Carvalho F. (2012). Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes. Br J Pharmacol 165:1017–1033.
   PubMedGoogle Scholar
• Basu S, Senior R, Raval U, van der Does R, Bruckner T, Lahiri A. (1997). Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial. Circulation 96:183–191.
   PubMed Web of Science ®Google Scholar
• Battaglia G, Brooks BP, Kulsakdinun C, De Souza EB. (1988). Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites. Eur J Pharmacol 149:159–163.
   PubMed Web of Science ®Google Scholar
• Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB. (2005). N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’). Neuropsychopharmacology 30:550–560.
   PubMed Web of Science ®Google Scholar
• Baumann MH, Wang X, Rothman RB. (2007). 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology (Berl) 189:407–424.
   PubMed Web of Science ®Google Scholar
• Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E. (2000). Ecstasy-induced toxicity in rat liver. Liver 20:8–15.
   PubMedGoogle Scholar
• Blessing WW, Seaman B, Pedersen NP, Ootsuka Y. (2003). Clozapine reverses hyperthermia and sympathetically mediated cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (ecstasy) in rabbits and rats. J Neurosci 23:6385–6391.
   Google Scholar
• Blessing WW, Zilm A, Ootsuka Y. (2006). Clozapine reverses increased brown adipose tissue thermogenesis induced by 3,4-methylenedioxymethamphetamine and by cold exposure in conscious rats. Neuroscience 141:2067–2073.
   Google Scholar
• Boyer EW, Shannon M. (2005). The serotonin syndrome. N Engl J Med 352:1112–1120.
   PubMed Web of Science ®Google Scholar
• Boyle NT, Connor TJ. (2010). Methylenedioxymethamphetamine (‘Ecstasy’)-induced immunosuppression: a cause for concern? Br J Pharmacol 161:17–32.
   PubMed Web of Science ®Google Scholar
• Brodde OE. (2008). β-1 and β-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 117:1–29.
   PubMed Web of Science ®Google Scholar
• Brogden RN, Sorkin EM. (1990). Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. Drugs 40:903–949.
   PubMed Web of Science ®Google Scholar
• Capela JP, Ruscher K, Lautenschlager M, Freyer D, Dirnagl U, Gaio AR, Bastos ML, Meisel A, Carvalho F. (2006). Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia. Neuroscience 139:1069–1081.
   PubMed Web of Science ®Google Scholar
• Capela JP, Fernandes E, Remião F, Bastos ML, Meisel A, Carvalho F. (2007a). Ecstasy induces apoptosis via 5-HT(2A)-receptor stimulation in cortical neurons. Neurotoxicology 28:868–875.
   PubMed Web of Science ®Google Scholar
• Capela JP, Macedo C, Branco PS, Ferreira LM, Lobo AM, Fernandes E, Remião F, Bastos ML, Dirnagl U, Meisel A, Carvalho F. (2007b). Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience 146:1743–1757.
   PubMed Web of Science ®Google Scholar
• Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F. (2009). Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39:210–271.
   PubMed Web of Science ®Google Scholar
• Carvalho M, Remião F, Milhazes N, Borges F, Fernandes E, Carvalho F, Bastos ML. (2004a). The toxicity of N-methyl-α-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine. Toxicology 200:193–203.
   PubMed Web of Science ®Google Scholar
• Carvalho M, Remião F, Milhazes N, Borges F, Fernandes E, Monteiro Mdo C, Gonçalves MJ, Seabra V, Amado F, Carvalho F, Bastos ML. (2004b). Metabolism is required for the expression of ecstasy-induced cardiotoxicity in vitro. Chem Res Toxicol 17:623–632.
   PubMed Web of Science ®Google Scholar
• Carvalho M, Pontes H, Remião F, Bastos ML, Carvalho F. (2010). Mechanisms underlying the hepatotoxic effects of ecstasy. Curr Pharm Biotechnol 11:476–495.
   PubMed Web of Science ®Google Scholar
• Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L. (2012). Toxicity of amphetamines: an update. Arch Toxicol 86:1167–1231.
   PubMed Web of Science ®Google Scholar
• Chu T, Kumagai Y, DiStefano EW, Cho AK. (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.
   PubMed Web of Science ®Google Scholar
• Colado MI, Williams JL, Green AR. (1995). The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype. Br J Pharmacol 115:1281–1289.
   PubMed Web of Science ®Google Scholar
• Colado MI, O’Shea E, Granados R, Esteban B, Martín AB, Green AR. (1999). Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration. Br J Pharmacol 126:911–924.
   PubMed Web of Science ®Google Scholar
• Connor TJ, Dennedy MC, Harkin A, Kelly JP. (2001). Methylenedioxymethamphetamine-induced suppression of interleukin-1β and tumour necrosis factor-α is not mediated by serotonin. Eur J Pharmacol 418:147–152.
   PubMedGoogle Scholar
• Copeland J, Dillon P, Gascoigne M. (2006). Ecstasy and the concomitant use of pharmaceuticals. Addict Behav 31:367–370.
   PubMed Web of Science ®Google Scholar
• Crespi D, Mennini T, Gobbi M. (1997). Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by (+)-amphetamine, 3,4-methylendioxymethamphetamine, p-chloroamphetamine and (+)-fenfluramine. Br J Pharmacol 121:1735–1743.
   PubMed Web of Science ®Google Scholar
• Cuyàs E, Verdejo-García A, Fagundo AB, Khymenets O, Rodríguez J, Cuenca A, de Sola Llopis S, Langohr K, Peña-Casanova J, Torrens M, Martín-Santos R, Farré M, de la Torre R. (2011). The influence of genetic and environmental factors among MDMA users in cognitive performance. PLoS ONE 6:e27206.
   Google Scholar
• D’Souza UM, Craig IW. (2006). Functional polymorphisms in dopamine and serotonin pathway genes. Hum Mutat 27:1–13.
   PubMed Web of Science ®Google Scholar
• D’Souza UM, Craig IW. (2008). Functional genetic polymorphisms in serotonin and dopamine gene systems and their significance in behavioural disorders. Prog Brain Res 172:73–98.
   PubMed Web of Science ®Google Scholar
• Daly AK. (2003). Pharmacogenetics of the major polymorphic metabolizing enzymes. Fundam Clin Pharmacol 17:27–41.
   PubMed Web of Science ®Google Scholar
• de la Torre R, Farre M, Ortuno J, Mas M, Brenneisen R, Roset PN, Segura J, Cami J. (2000). Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol 49:104–109.
   PubMed Web of Science ®Google Scholar
• de la Torre R, Farre M, Mathuna BO, Roset PN, Pizarro N, Segura M, Torrens M, Ortuno J, Pujadas M, Cami J. (2005). MDMA (ecstasy) pharmacokinetics in a CYP2D6 poor metaboliser and in nine CYP2D6 extensive metabolisers. Eur J Clin Pharmacol 61:551–554.
   PubMed Web of Science ®Google Scholar
• Devlin RJ, Henry JA. (2008). Clinical review: Major consequences of illicit drug consumption. Crit Care 12:202.
   PubMed Web of Science ®Google Scholar
• Dickinson SD, Sabeti J, Larson GA, Giardina K, Rubinstein M, Kelly MA, Grandy DK, Low MJ, Gerhardt GA, Zahniser NR. (1999). Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but no changes in dopamine release in dorsal striatum. J Neurochem 72:148–156.
   PubMedGoogle Scholar
• Docherty JR, Green AR. (2010). The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. Br J Pharmacol 160:1029–1044.
   Google Scholar
• EMCDDA. (2010). Annual report 2010. The state of the drugs problem in Europe. Lisbon: European Monitoring Centre for Drugs and Drug Addiction.
   Google Scholar
• Erives GV, Lau SS, Monks TJ. (2008). Accumulation of neurotoxic thioether metabolites of 3,4-(+/-)-methylenedioxymethamphetamine in rat brain. J Pharmacol Exp Ther 324:284–291.
   PubMed Web of Science ®Google Scholar
• Escubedo E, Abad S, Torres I, Camarasa J, Pubill D. (2011). Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its metabolite α-methyldopamine on key targets of MDMA neurotoxicity. Neurochem Int 58:92–101.
   PubMedGoogle Scholar
• Esteban B, O’Shea E, Camarero J, Sanchez V, Green AR, Colado MI. (2001). 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose. Psychopharmacology (Berl) 154:251–260.
   PubMed Web of Science ®Google Scholar
• Fagundo AB, Cuyàs E, Verdejo-Garcia A, Khymenets O, Langohr K, Martín-Santos R, Farré M, de la Torre R. (2010). The influence of 5-HTT and COMT genotypes on verbal fluency in ecstasy users. J Psychopharmacol (Oxford) 24:1381–1393.
   PubMedGoogle Scholar
• Farré M, de la Torre R, Mathúna BO, Roset PN, Peiró AM, Torrens M, Ortuño J, Pujadas M, Camí J. (2004). Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics. Psychopharmacology (Berl) 173:364–375.
   PubMed Web of Science ®Google Scholar
• Farré M, Abanades S, Roset PN, Peiró AM, Torrens M, O’Mathúna B, Segura M, de la Torre R. (2007). Pharmacological interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: pharmacological effects and pharmacokinetics. J Pharmacol Exp Ther 323:954–962.
   PubMed Web of Science ®Google Scholar
• Finnegan KT, Skratt JJ, Irwin I, Langston JW. (1989). The N-methyl-D-aspartate (NMDA) receptor antagonist, dextrorphan, prevents the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neurosci Lett 105:300–306.
   PubMedGoogle Scholar
• Garcia-Ratés S, Camarasa J, Sánchez-García AI, Gandía L, Escubedo E, Pubill D. (2010). The effects of 3,4-methylenedioxymethamphetamine (MDMA) on nicotinic receptors: intracellular calcium increase, calpain/caspase 3 activation, and functional upregulation. Toxicol Appl Pharmacol 244:344–353.
   PubMedGoogle Scholar
• Gilhooly TC, Daly AK. (2002). CYP2D6 deficiency, a factor in ecstasy related deaths? Br J Clin Pharmacol 54:69–70.
   PubMedGoogle Scholar
• Ginsberg G, Smolenski S, Hattis D, Guyton KZ, Johns DO, Sonawane B. (2009). Genetic Polymorphism in Glutathione Transferases (GST): Population distribution of GSTM1, T1, and P1 conjugating activity. J Toxicol Environ Health B Crit Rev 12:389–439.
   PubMed Web of Science ®Google Scholar
• Ginsberg G, Guyton K, Johns D, Schimek J, Angle K, Sonawane B. (2010). Genetic polymorphism in metabolism and host defense enzymes: implications for human health risk assessment. Crit Rev Toxicol 40:575–619.
   PubMed Web of Science ®Google Scholar
• Gough B, Ali SF, Slikker W JR, Holson RR. (1991). Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. Pharmacol Biochem Behav 39:619–623.
   PubMed Web of Science ®Google Scholar
• Gouzoulis-Mayfrank E, Daumann J. (2006). The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J Psychopharmacol (Oxford) 20:188–193.
   PubMed Web of Science ®Google Scholar
• Granado N, Escobedo I, O’Shea E, Colado I, Moratalla R. (2008a). Early loss of dopaminergic terminals in striosomes after MDMA administration to mice. Synapse 62:80–84.
   PubMedGoogle Scholar
• Granado N, O’Shea E, Bove J, Vila M, Colado MI, Moratalla R. (2008b). Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice. J Neurochem 107:1102–1112.
   PubMedGoogle Scholar
• Granado N, Ares-Santos S, Oliva I, O’Shea E, Martin ED, Colado MI, Moratalla R. (2011). Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA. Neurobiol Dis 42:391–403.
   PubMed Web of Science ®Google Scholar
• Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI. (2003). The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55:463–508.
   PubMed Web of Science ®Google Scholar
• Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL. (1999). Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. Am J Med Genet 88:83–87.
   PubMed Web of Science ®Google Scholar
• Grunau BE, Wiens MO, Brubacher JR. (2010). Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. CJEM 12:435–442.
   PubMedGoogle Scholar
• Haavik J, Blau N, Thöny B. (2008). Mutations in human monoamine-related neurotransmitter pathway genes. Hum Mutat 29:891–902.
   PubMed Web of Science ®Google Scholar
• Hagino Y, Takamatsu Y, Yamamoto H, Iwamura T, Murphy DL, Uhl GR, Sora I, Ikeda K. (2011). Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters. Curr Neuropharmacol 9:91–95.
   PubMedGoogle Scholar
• Han DD, Gu HH. (2006). Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 6:6.
   PubMedGoogle Scholar
• Hashimoto K. (1993). Effects of benzylpiperazine derivatives on the acute effects of 3,4-methylenedioxymethamphetamine in rat brain. Neurosci Lett 152:17–20.
   PubMed Web of Science ®Google Scholar
• Henry JA, Hill IR. (1998). Fatal interaction between ritonavir and MDMA. Lancet 352:1751–1752.
   PubMed Web of Science ®Google Scholar
• Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ. (2001). Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos 29:100–102.
   PubMed Web of Science ®Google Scholar
• Hewitt KE, Green AR. (1994). Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA (‘Ecstasy’) to rats. Neuropharmacology 33:1589–1595.
   PubMed Web of Science ®Google Scholar
• Heydari A, Yeo KR, Lennard MS, Ellis SW, Tucker GT, Rostami-Hodjegan A. (2004). Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine. Drug Metab Dispos 32:1213–1217.
   PubMed Web of Science ®Google Scholar
• Hill S, Thomas SH. (2008). Recreational drug toxicity. Clin Med 8:99–103.
   PubMedGoogle Scholar
• Hondebrink L, Meulenbelt J, Meijer M, van den Berg M, Westerink RH. (2011a). High concentrations of MDMA (‘ecstasy’) and its metabolite MDA inhibit calcium influx and depolarization-evoked vesicular dopamine release in PC12 cells. Neuropharmacology 61:202–208.
   PubMedGoogle Scholar
• Hondebrink L, Meulenbelt J, van Kleef RG, van den Berg M, Westerink RH. (2011b). Modulation of human GABAA receptor function: a novel mode of action of drugs of abuse. Neurotoxicology 32:823–827.
   PubMed Web of Science ®Google Scholar
• Hondebrink L, Meulenbelt J, Rietjens SJ, Meijer M, Westerink RH. (2012). Methamphetamine, amphetamine, MDMA (‘ecstasy’), MDA and mCPP modulate electrical and cholinergic input in PC12 cells. Neurotoxicology 33:255–260.
   PubMedGoogle Scholar
• Hysek CM, Vollenweider FX, Liechti ME. (2010). Effects of a β-blocker on the cardiovascular response to MDMA (Ecstasy). Emerg Med J 27:586–589.
   Google Scholar
• Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME. (2011). The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (“ecstasy”) in humans. Clin Pharmacol Ther 90:246–255.
   PubMed Web of Science ®Google Scholar
• Hysek CM, Brugger R, Simmler LD, Bruggisser M, Donzelli M, Grouzmann E, Hoener MC, Liechti ME. (2012a). Effects of the a2-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers. J Pharmacol Exp Ther 340:286–294.
   PubMed Web of Science ®Google Scholar
• Hysek C, Schmid Y, Rickli A, Simmler L, Donzelli M, Grouzmann E, Liechti M. (2012b). Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans. Br J Pharmacol 166:2277–2288.
   PubMed Web of Science ®Google Scholar
• Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME. (2012c). Duloxetine inhibits effects of MDMA (“ecstasy”) in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS ONE 7:e36476.
   PubMed Web of Science ®Google Scholar
• Jones DC, Duvauchelle C, Ikegami A, Olsen CM, Lau SS, de la Torre R, Monks TJ. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther 313:422–431.
   PubMed Web of Science ®Google Scholar
• Kaminer Y, Goldberg P, Connor DF. (2010). Psychotropic medications and substances of abuse interactions in youth. Subst Abus 31:53–57.
   PubMed Web of Science ®Google Scholar
• Kanthasamy A, Sprague JE, Shotwell JR, Nichols DE. (2002). Unilateral infusion of a dopamine transporter antisense into the substantia nigra protects against MDMA-induced serotonergic deficits in the ipsilateral striatum. Neuroscience 114:917–924.
   PubMedGoogle Scholar
• Kasai M, Shioda K, Nisijima K, Yoshino T, Iwamura T, Kato S. (2011). The effects of mirtazapine and fluoxetine on hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neurosci Lett 499:24–27.
   PubMedGoogle Scholar
• Kaskey GB. (1992). Possible interaction between an MAOI and “ecstasy”. Am J Psychiatry 149:411–412.
   PubMedGoogle Scholar
• Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T. (2011). Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Br J Pharmacol 164:1949–1958.
   PubMed Web of Science ®Google Scholar
• Kelsey RM, Alpert BS, Dahmer MK, Krushkal J, Quasney MW. (2010). β-adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults. Psychophysiology 47:863–873.
   PubMedGoogle Scholar
• Kelsey RM, Alpert BS, Dahmer MK, Krushkal J, Quasney MW. (2012). α-adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults. Psychophysiology 49:401–412.
   PubMedGoogle Scholar
• Koch S, Galloway MP. (1997). MDMA induced dopamine release in vivo: role of endogenous serotonin. J Neural Transm 104:135–146.
   PubMed Web of Science ®Google Scholar
• Kreth K, Kovar K, Schwab M, Zanger UM. (2000). Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol 59:1563–1571.
   PubMed Web of Science ®Google Scholar
• Lavelle A, Honner V, Docherty JR. (1999). Investigation of the prejunctional α2-adrenoceptor mediated actions of MDMA in rat atrium and vas deferens. Br J Pharmacol 128:975–980.
   PubMed Web of Science ®Google Scholar
• Leonardi ET, Azmitia EC. (1994). MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacology 10:231–238.
   Google Scholar
• Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Baumann C, Gamma A, Vollenweider FX. (2000a). Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram. Neuropsychopharmacology 22:513–521.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX. (2000b). Psychological and physiological effects of MDMA (“Ecstasy”) after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans. Neuropsychopharmacology 23:396–404.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Vollenweider FX. (2000a). Acute psychological and physiological effects of MDMA (“Ecstasy”) after haloperidol pretreatment in healthy humans. Eur Neuropsychopharmacol 10:289–295.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Vollenweider FX. (2000b). The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers. J Psychopharmacol (Oxford) 14:269–274.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Gamma A, Vollenweider FX. (2001). Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl) 154:161–168.
   PubMed Web of Science ®Google Scholar
• Liechti ME, Vollenweider FX. (2001). Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies. Hum Psychopharmacol 16:589–598.
   PubMed Web of Science ®Google Scholar
• Lundström K, Tenhunen J, Tilgmann C, Karhunen T, Panula P, Ulmanen I. (1995). Cloning, expression and structure of catechol-O-methyltransferase. Biochim Biophys Acta 1251:1–10.
   PubMed Web of Science ®Google Scholar
• Malberg JE, Sabol KE, Seiden LS. (1996). Co-administration of MDMA with drugs that protect against MDMA neurotoxicity produces different effects on body temperature in the rat. J Pharmacol Exp Ther 278:258–267.
   PubMed Web of Science ®Google Scholar
• Malpass A, White JM, Irvine RJ, Somogyi AA, Bochner F. (1999). Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats. Pharmacol Biochem Behav 64:29–34.
   PubMed Web of Science ®Google Scholar
• Männistö PT, Kaakkola S. (1999). Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev 51:593–628.
   PubMed Web of Science ®Google Scholar
• Martín-Santos R, Torrens M, Poudevida S, Langohr K, Cuyás E, Pacifici R, Farré M, Pichini S, de la Torre R. (2010). 5-HTTLPR polymorphism, mood disorders and MDMA use in a 3-year follow-up study. Addict Biol 15:15–22.
   PubMedGoogle Scholar
• Marwood JF. (1994). Influence of α 1-adrenoceptor antagonism of ketanserin on the nature of its 5-HT2 receptor antagonism. Clin Exp Pharmacol Physiol 21:955–961.
   PubMedGoogle Scholar
• McCann UD, Ricaurte GA. (1993). Reinforcing subjective effects of (+/-) 3,4-methylenedioxymethamphetamine (“ecstasy”) may be separable from its neurotoxic actions: clinical evidence. J Clin Psychopharmacol 13:214–217.
   PubMed Web of Science ®Google Scholar
• Mechan AO, Esteban B, O’Shea E, Elliott JM, Colado MI, Green AR. (2002). The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats. Br J Pharmacol 135:170–180.
   PubMed Web of Science ®Google Scholar
• Meyer MR, Peters FT, Maurer HH. (2008). The role of human hepatic cytochrome P450 isozymes in the metabolism of racemic 3,4-methylenedioxy-methamphetamine and its enantiomers. Drug Metab Dispos 36:2345–2354.
   PubMed Web of Science ®Google Scholar
• Milhazes N, Cunha-Oliveira T, Martins P, Garrido J, Oliveira C, Rego AC, Borges F. (2006). Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine (“ecstasy”) and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship. Chem Res Toxicol 19:1294–1304.
   PubMed Web of Science ®Google Scholar
• Millan MJ, Gobert A, Lejeune F, Newman-Tancredi A, Rivet JM, Auclair A, Peglion JL. (2001). S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther 298:565–580.
   PubMed Web of Science ®Google Scholar
• Mlinar B, Corradetti R. (2003). Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5-HT1B receptors located on CA1 pyramidal neurons. Eur J Neurosci 18:1559–1571.
   PubMedGoogle Scholar
• Mohamed WM, Ben Hamida S, Cassel JC, de Vasconcelos AP, Jones BC. (2011). MDMA: interactions with other psychoactive drugs. Pharmacol Biochem Behav 99:759–774.
   PubMed Web of Science ®Google Scholar
• Monks TJ, Jones DC, Bai F, Lau SS. (2004). The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicity. Ther Drug Monit 26:132–136.
   PubMed Web of Science ®Google Scholar
• Morgan MJ. (2000). Ecstasy (MDMA): a review of its possible persistent psychological effects. Psychopharmacology (Berl) 152:230–248.
   PubMed Web of Science ®Google Scholar
• Morini R, Mlinar B, Baccini G, Corradetti R. (2011). Enhanced hippocampal long-term potentiation following repeated MDMA treatment in Dark-Agouti rats. Eur Neuropsychopharmacol 21:80–91.
   PubMedGoogle Scholar
• Mueller M, Yuan J, Felim A, Neudörffer A, Peters FT, Maurer HH, McCann UD, Largeron M, Ricaurte GA. (2009). Further studies on the role of metabolites in (+/-)-3,4-methylenedioxymethamphetamine-induced serotonergic neurotoxicity. Drug Metab Dispos 37:2079–2086.
   PubMedGoogle Scholar
• Murnane KS, Kimmel HL, Rice KC, Howell LL. (2012). The neuropharmacology of prolactin secretion elicited by 3,4-methylenedioxymethamphetamine (“ecstasy”): a concurrent microdialysis and plasma analysis study. Horm Behav 61:181–190.
   PubMedGoogle Scholar
• Murphy PN, Wareing M, Fisk JE, Montgomery C. (2009). Executive working memory deficits in abstinent ecstasy/MDMA users: a critical review. Neuropsychobiology 60:159–175.
   PubMedGoogle Scholar
• Nagata K, Yamazoe Y. (2000). Pharmacogenetics of sulfotransferase. Annu Rev Pharmacol Toxicol 40:159–176.
   PubMed Web of Science ®Google Scholar
• Nash JF Jr, Meltzer HY, Gudelsky GA. (1988). Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. J Pharmacol Exp Ther 245:873–879.
   Google Scholar
• Nash JF. (1990). Ketanserin pretreatment attenuates MDMA-induced dopamine release in the striatum as measured by in vivo microdialysis. Life Sci 47:2401–2408.
   PubMed Web of Science ®Google Scholar
• Nash JF, Meltzer HY, Gudelsky GA. (1990). Effect of 3,4-methylenedioxymethamphetamine on 3,4-dihydroxyphenylalanine accumulation in the striatum and nucleus accumbens. J Neurochem 54:1062–1067.
   PubMed Web of Science ®Google Scholar
• Nash JF, Brodkin J. (1991). Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors. J Pharmacol Exp Ther 259:820–825.
   PubMed Web of Science ®Google Scholar
• Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA. (1994). Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors. Neurosci Lett 177:111–115.
   PubMed Web of Science ®Google Scholar
• O’Donohoe A, O’Flynn K, Shields K, Hawi Z, Gill M. (1998). MDMA toxicity:no evidence for a major influence of metabolic genotype at CYP2D6. Addiction Biol 3:309–314.
   PubMed Web of Science ®Google Scholar
• O’Mathúna B, Farré M, Rostami-Hodjegan A, Yang J, Cuyàs E, Torrens M, Pardo R, Abanades S, Maluf S, Tucker GT, de la Torre R. (2008). The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans. J Clin Psychopharmacol 28:523–529.
   PubMed Web of Science ®Google Scholar
• Oesterheld JR, Armstrong SC, Cozza KL. (2004). Ecstasy: pharmacodynamic and pharmacokinetic interactions. Psychosomatics 45:84–87.
   PubMed Web of Science ®Google Scholar
• Orio L, O’Shea E, Sanchez V, Pradillo JM, Escobedo I, Camarero J, Moro MA, Green AR, Colado MI. (2004). 3,4-Methylenedioxymethamphetamine increases interleukin-1β levels and activates microglia in rat brain: studies on the relationship with acute hyperthermia and 5-HT depletion. J Neurochem 89:1445–1453.
   PubMedGoogle Scholar
• Paris JM, Cunningham KA. (1992). Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4-methylenedioxymethamphetamine (MDMA). Brain Res Bull 28:115–119.
   PubMedGoogle Scholar
• Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC. (2006). Storage of spatial information by the maintenance mechanism of LTP. Science 313:1141–1144.
   PubMed Web of Science ®Google Scholar
• Perfetti X, O’Mathúna B, Pizarro N, Cuyàs E, Khymenets O, Almeida B, Pellegrini M, Pichini S, Lau SS, Monks TJ, Farré M, Pascual JA, Joglar J, de la Torre R. (2009). Neurotoxic thioether adducts of 3,4-methylenedioxymethamphetamine identified in human urine after ecstasy ingestion. Drug Metab Dispos 37:1448–1455.
   PubMed Web of Science ®Google Scholar
• Pifl C, Nagy G, Berényi S, Kattinger A, Reither H, Antus S. (2005). Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. J Pharmacol Exp Ther 314:346–354.
   PubMedGoogle Scholar
• Pilgrim JL, Gerostamoulos D, Drummer OH. (2011). Deaths involving MDMA and the concomitant use of pharmaceutical drugs. J Anal Toxicol 35:219–226.
   PubMed Web of Science ®Google Scholar
• Raffel DM, Chen W. (2004). Binding of [3H]mazindol to cardiac norepinephrine transporters: kinetic and equilibrium studies. Naunyn Schmiedebergs Arch Pharmacol 370:9–16.
   PubMedGoogle Scholar
• Reneman L, Schilt T, de Win MM, Booij J, Schmand B, van den Brink W, Bakker O. (2006). Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users. J Psychopharmacol (Oxford) 20:389–399.
   PubMed Web of Science ®Google Scholar
• Roiser JP, Cook LJ, Cooper JD, Rubinsztein DC, Sahakian BJ. (2005). Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. Am J Psychiatry 162:609–612.
   PubMedGoogle Scholar
• Rosenson J, Smollin C, Sporer KA, Blanc P, Olson KR. (2007). Patterns of ecstasy-associated hyponatremia in California. Ann Emerg Med 49:164–71, 171.e1.
   PubMed Web of Science ®Google Scholar
• Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41.
   PubMed Web of Science ®Google Scholar
• Rudnick G, Wall SC. (1992). The molecular mechanism of “ecstasy” [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc Natl Acad Sci USA 89:1817–1821.
   PubMed Web of Science ®Google Scholar
• Runkel F, Brüss M, Nöthen MM, Stöber G, Propping P, Bönisch H. (2000). Pharmacological properties of naturally occurring variants of the human norepinephrine transporter. Pharmacogenetics 10:397–405.
   PubMedGoogle Scholar
• Sanchez V, Camarero J, Esteban B, Peter MJ, Green AR, Colado MI. (2001). The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)-induced degeneration of 5-HT nerve endings in rat brain. Br J Pharmacol 134:46–57.
   PubMed Web of Science ®Google Scholar
• Schenk S, Harper DN, Do J. (2011). Novel object recognition memory: measurement issues and effects of MDMA self-administration following short inter-trial intervals. J Psychopharmacol (Oxford) 25:1043–1052.
   PubMedGoogle Scholar
• Schmidt CJ. (1987). Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J Pharmacol Exp Ther 240:1–7.
   PubMed Web of Science ®Google Scholar
• Schmidt CJ, Taylor VL. (1987). Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol 36:4095–4102.
   PubMed Web of Science ®Google Scholar
• Schmidt CJ, Levin JA, Lovenberg W. (1987). In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. Biochem Pharmacol 36:747–755.
   PubMed Web of Science ®Google Scholar
• Schmidt CJ, Black CK, Taylor VL. (1990). Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine. Eur J Pharmacol 181:59–70.
   PubMedGoogle Scholar
• Schmidt CJ, Sullivan CK, Fadayel GM. (1994). Blockade of striatal 5-hydroxytryptamine2 receptors reduces the increase in extracellular concentrations of dopamine produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine. J Neurochem 62:1382–1389.
   PubMed Web of Science ®Google Scholar
• Schwaninger AE, Meyer MR, Zapp J, Maurer HH. (2009). The role of human UDP-glucuronyltransferases on the formation of the methylenedioxymethamphetamine (ecstasy) phase II metabolites R- and S-3-methoxymethamphetamine 4-O-glucuronides. Drug Metab Dispos 37:2212–2220.
   PubMed Web of Science ®Google Scholar
• Schwaninger AE, Meyer MR, Barnes AJ, Kolbrich-Spargo EA, Gorelick DA, Goodwin RS, Huestis MA, Maurer HH. (2011). Urinary excretion kinetics of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its phase I and phase II metabolites in humans following controlled MDMA administration. Clin Chem 57:1748–1756.
   PubMedGoogle Scholar
• Segura M, Farré M, Pichini S, Peiró AM, Roset PN, Ramírez A, Ortuño J, Pacifici R, Zuccaro P, Segura J, de la Torre R. (2005). Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe. Clin Pharmacokinet 44:649–660.
   PubMed Web of Science ®Google Scholar
• Sevrioukova IF, Poulos TL. (2010). Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci USA 107:18422–18427.
   PubMed Web of Science ®Google Scholar
• Shankaran M, Gudelsky GA. (1998). Effect of 3,4-methylenedioxymethamphetamine (MDMA) on hippocampal dopamine and serotonin. Pharmacol Biochem Behav 61:361–366.
   PubMed Web of Science ®Google Scholar
• Shankaran M, Yamamoto BK, Gudelsky GA. (1999a). Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. Eur J Pharmacol 385:103–110.
   PubMed Web of Science ®Google Scholar
• Shankaran M, Yamamoto BK, Gudelsky GA. (1999b). Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum. J Neurochem 72:2516–2522.
   PubMed Web of Science ®Google Scholar
• Shih JC, Chen K, Ridd MJ. (1999). Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 22:197–217.
   PubMed Web of Science ®Google Scholar
• Shioda K, Nisijima K, Yoshino T, Kuboshima K, Iwamura T, Yui K, Kato S. (2008). Risperidone attenuates and reverses hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neurotoxicology 29:1030–1036.
   PubMedGoogle Scholar
• Shoda T, Fukuhara K, Goda Y, Okuda H. (2009). 4-Hydroxy-3-methoxymethamphetamine glucuronide as a phase II metabolite of 3,4-methylenedioxymethamphetamine: enzyme-assisted synthesis and involvement of human hepatic uridine 5′-diphosphate-glucuronosyltransferase 2B15 in the glucuronidation. Chem Pharm Bull 57:472–475.
   PubMed Web of Science ®Google Scholar
• Simmler LD, Hysek CM, Liechti ME. (2011). Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab 96:2844–2850.
   PubMed Web of Science ®Google Scholar
• Smilkstein MJ, Smolinske SC, Rumack BH. (1987). A case of MAO inhibitor/MDMA interaction: agony after ecstasy. J Toxicol Clin Toxicol 25:149–159.
   PubMed Web of Science ®Google Scholar
• Sprague JE, Moze P, Caden D, Rusyniak DE, Holmes C, Goldstein DS, Mills EM. (2005). Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model. Crit Care Med 33:1311–1316.
   PubMed Web of Science ®Google Scholar
• Sprague JE, Nichols DE. (2005). Neurotoxicity of MDMA (ecstasy): beyond metabolism. Trends Pharmacol Sci 26:59–60; author reply 60.
   PubMedGoogle Scholar
• Stein DJ, Rink J. (1999). Effects of “Ecstasy” blocked by serotonin reuptake inhibitors. J Clin Psychiatry 60:485.
   PubMedGoogle Scholar
• Stone DM, Stahl DC, Hanson GR, Gibb JW. (1986). The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. Eur J Pharmacol 128:41–48.
   PubMed Web of Science ®Google Scholar
• Stone DM, Merchant KM, Hanson GR, Gibb JW. (1987). Immediate and long-term effects of 3,4-methylenedioxymethamphetamine on serotonin pathways in brain of rat. Neuropharmacology 26:1677–1683.
   PubMed Web of Science ®Google Scholar
• Tancer M, Johanson CE. (2007). The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 189:565–573.
   PubMed Web of Science ®Google Scholar
• Trojan A, Vergopoulos A, Breitenstein U, Seifert B, Rageth C, Joechle W. (2012). The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer. Breast Care (Basel) 7:25–31.
   PubMedGoogle Scholar
• Tucker GT, Lennard MS, Ellis SW, Woods HF, Cho AK, Lin LY, Hiratsuka A, Schmitz DA, Chu TY. (1994). The demethylenation of methylenedioxymethamphetamine (“ecstasy”) by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 47:1151–1156.
   PubMed Web of Science ®Google Scholar
• Turnpenny P, Fraier D. (2009). Sensitive quantitation of reboxetine enantiomers in rat plasma and brain, using an optimised reverse phase chiral LC-MS/MS method. J Pharm Biomed Anal 49:133–139.
   PubMed Web of Science ®Google Scholar
• Upreti VV, Eddington ND. (2008). Fluoxetine pretreatment effects pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, ECSTASY) in rat. J Pharm Sci 97:1593–1605.
   PubMed Web of Science ®Google Scholar
• van Nieuwenhuijzen PS, Long LE, Hunt GE, Arnold JC, McGregor IS. (2010). Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. Psychopharmacology (Berl) 212:663–674.
   PubMedGoogle Scholar
• van Thriel C, Westerink RH, Beste C, Bale AS, Lein PJ, Leist M. (2012). Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts. Neurotoxicology 33:911–924.
   PubMedGoogle Scholar
• Verrico CD, Miller GM, Madras BK. (2007). MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl) 189:489–503.
   PubMed Web of Science ®Google Scholar
• von Möllendorff E, Reiff K, Neugebauer G. (1987). Pharmacokinetics and bioavailability of carvedilol, a vasodilating β-blocker. Eur J Clin Pharmacol 33:511–513.
   PubMed Web of Science ®Google Scholar
• von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI. (1998). Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci 87:1184–1189.
   PubMed Web of Science ®Google Scholar
• Vuori E, Henry JA, Ojanperä I, Nieminen R, Savolainen T, Wahlsten P, Jäntti M. (2003). Death following ingestion of MDMA (ecstasy) and moclobemide. Addiction 98:365–368.
   PubMed Web of Science ®Google Scholar
• Wall SC, Gu H, Rudnick G. (1995). Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 47:544–550.
   PubMed Web of Science ®Google Scholar
• Whitlock JR, Heynen AJ, Shuler MG, Bear MF. (2006). Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097.
   PubMed Web of Science ®Google Scholar
• Wichems CH, Hollingsworth CK, Bennett BA. (1995). Release of serotonin induced by 3,4-methylenedioxymethamphetamine (MDMA) and other substituted amphetamines in cultured fetal raphe neurons: further evidence for calcium-independent mechanisms of release. Brain Res 695:10–18.
   PubMedGoogle Scholar
• Yang J, Jamei M, Heydari A, Yeo KR, de la Torre R, Farré M, Tucker GT, Rostami-Hodjegan A. (2006). Implications of mechanism-based inhibition of CYP2D6 for the pharmacokinetics and toxicity of MDMA. J Psychopharmacol (Oxford) 20:842–849.
   PubMed Web of Science ®Google Scholar
• Zhang X, Beaulieu JM, Gainetdinov RR, Caron MG. (2006). Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2. Cell Mol Life Sci 63:6–11.
   PubMed Web of Science ®Google Scholar
• Zhou SF, Liu JP, Chowbay B. (2009). Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41:89–295.
   PubMed Web of Science ®Google Scholar
• Zhu BT. (2002). Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. Curr Drug Metab 3:321–349.
   PubMed Web of Science ®Google Scholar