Fatal poisoning by MDMA (ecstasy) and MDEA: A case report

Fineschi, Vittorio; Masti, Alessandra

doi:10.1007/bf01369826

Cited by 58 publications

(25 citation statements)

References 21 publications

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“…DIC and rhabdomyolysis are frequent clinical consequences of ecstasy abuse (and of amphetamines in general), resulting in varying degrees of microvascular obstruction due to fibrin-platelet or myoglobin deposition, respectively (Fahal et al 1992;Fineschi and Masti 1996;Cunningham 1997). This process may result in sudden renal ischaemia and acute tubular necrosis.…”

mentioning

confidence: 97%

Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells

Carvalho

Hawksworth

Milhazes

et al. 2002

Archives of Toxicology

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The metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has recently been implicated in the mechanisms underlying ecstasy-induced neurotoxicity and hepatotoxicity. However, its potential role in ecstasy-induced kidney toxicity has yet to be investigated. Thus, primary cultures of rat and human renal proximal tubular cells (PTCs) were used to investigate the cytotoxicity induced by MDMA and its metabolites methylenedioxyamphetamine (MDA), alpha-methyldopamine (alpha-MeDA), and the glutathione (GSH) conjugates 5-(glutathion- S-yl)-alpha-MeDA and 2,5- bis(glutathion- S-yl)-alpha-MeDA. Cell viability was evaluated using the mitochondrial MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MDMA and MDA were not found to be toxic to either rat or human PTCs at any concentration tested (100-800 micro M). In contrast, 800 micro M alpha-MeDA caused 60% and 40% cell death in rat and human PTCs, respectively. Conjugation of alpha-MeDA with GSH resulted in the formation of even more potent nephrotoxicants. Thus, exposure of rat and human PTC monolayers to 400 micro M 5-(glutathion- S-yl)-alpha-MeDA caused approximately 80% and 70% cell death, respectively. 5-(Glutathion- S-yl)-alpha-MeDA (400 micro M) was more toxic than 2,5- bis(glutathion- S-yl)-alpha-MeDA to rat renal PTCs but equally potent in human renal PTCs. Pre-incubation of rat PTCs with either acivicin, an inhibitor of gamma-glutamyl transpeptidase (gamma-GT), or bestatin, an inhibitor of aminopeptidase M, resulted in increased toxicity of 5-(glutathion- S-yl)-alpha-MeDA but had no effect on 2,5- bis(glutathion- S-yl)-alpha-MeDA-mediated cytotoxicity. The present data provide evidence that metabolism is required for the expression of MDMA-induced renal toxicity in vitro. In addition, metabolism of 5-(glutathion- S-yl)-alpha-MeDA by gamma-GT and aminopeptidase M to the corresponding cystein- S-yl-glycine and/or cystein- S-yl conjugates is likely to be associated with detoxication of this compound. Thus, it appears that toxicity induced by thioether metabolites of ecstasy at the apical membrane of renal proximal tubular cells is the result of extracellular events, presumably redox cycling.

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mentioning

confidence: 97%

Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells

Carvalho

Hawksworth

Milhazes

et al. 2002

Archives of Toxicology

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“…-In severe cases this syndrome leads to rhabdomyolysis, disseminated intravascular coagulation (DIC), acute renal and eventually multiorgan failure (36,37,67,172,174,178), that require referral to an intensive care unit.…”

Section: Physical Complicationsmentioning

confidence: 99%

“…Table 5 summarizes 20 fatalities in which the presence of MDEA was toxicologically confirmed (2,4,26,33,36,37,39,70,93,106,130,178).…”

Section: Mdea-related Fatalitiesmentioning

confidence: 99%

The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)

Freudenmann

Spitzer

2004

CNS Drug Reviews

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This paper reviews the pharmacology and toxicology of 3,4-methylenedioxy-N-ethylamphetamine (MDEA, "eve"). MDEA is a ring-substituted amphetamine (RSA) like MDMA, its well known N-methyl analog. Both have become very popular substances of abuse in the techno-and house-music scene. They can evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and a positive emotional state as well as sympathomimetic physical effects. At present, the name "ecstasy" is no longer used only for MDMA, but for the whole group of RSAs (MDA, MDMA, MDEA and MBDB) as they are chemically and pharmacologically nearly identical; moreover, many ecstasy pills contain mixtures of the RSAs. Hence, for a selective review on MDEA, it is crucial to strictly differentiate between: 1) street and chemical names, and 2) studies with or without chemically defined substances. In order to present MDEA-specific information, the pharmacodynamics and kinetics are described on the basis of MDEA challenge studies in animals and humans. In the toxicology section, we present a collection of case reports on fatalities where MDEA was toxicologically confirmed. On the question of serotonergic neurotoxicity and possible long-term consequences, however, MDEA-specific information is available from animal studies only. The neurotoxic potential of MDEA in humans is difficult to estimate, as ecstasy users do not consume pure substances. For future research, challenge studies in animals using dosing regimens adapted to human consumption patterns are needed. Such challenge studies should directly compare individual RSAs. They will represent the most viable and fruitful approach to the resolution of the highly controversial issues of serotonergic neurotoxicity and its functional consequences.

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“…The consumption of these substances as ''party drugs,'' considered to be harmless by most young people, is alarming, especially if one considers their harmful effects on nerves, the liver, the kidneys and the brain. Fatal poisonings with and without the involvement of other toxicologically relevant substances have been reported [1][2][3][4][5][6][7][8]. Currently, there is an increasing number of publications dealing with drivers under the influence of methylenedioxyamphetamine-type drugs [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Development of a validated method for the simultaneous determination of amphetamine, methamphetamine and methylenedioxyamphetamines (MDA, MDMA, MDEA) in serum by GC-MS after derivatisation with perfluorooctanoyl chloride

et al. 2007

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A rapid and simple method for the simultaneous detection and quantitation of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxyethylamphetamine (MDEA) in human serum was developed and fully validated. Serum samples were extracted with cyclohexane, derivatised with perfluorooctanoyl chloride without prior evaporation of the solvent and analysed with gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode (SIM). For quantitation, deuterated analogues were used as the internal standards. The limit of detection (LOD) and lower limit of quantitation (LLOQ), bias and within-day and between-day precision were determined. LODs calculated as the average of the six calibration curves were below 5 ng/mL for all of the measured compounds; LLOQs obtained in the same manner were below 20 ng/mL, with the exception of MDA (24.1 ng/mL). The coefficients of variation were below 7% within series, 10% or less between series and the bias was below 8% for all compounds. The calibration curves were linear between the lower limits of quantitation and 800 ng/mL.

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Fatal poisoning by MDMA (ecstasy) and MDEA: A case report

Cited by 58 publications

References 21 publications

Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells

Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells

The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)

Development of a validated method for the simultaneous determination of amphetamine, methamphetamine and methylenedioxyamphetamines (MDA, MDMA, MDEA) in serum by GC-MS after derivatisation with perfluorooctanoyl chloride

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