Two Very Different Fatal Cases Associated with the Use of Methylenedioxyethylamphet-amine (MDEA): Eve as Deadly as Adam

Iwersen, Stefanie; Schmoldt, A.

doi:10.3109/15563659609013778

Cited by 16 publications

(12 citation statements)

References 19 publications

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“…Designer drugs are a serious problem worldwide, especially among young people, and in some cases they have resulted in fatal poisoning [1][2][3][4][5][6][7]. New designer drugs are created by changing the molecular structure of an existing drug.…”

Section: Introductionmentioning

confidence: 99%

Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Taniguchi

Yamamoto²,

Nishi³

2013

AJAC

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Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information available on how these new drugs are metabolized or their ability to inhibit the metabolism of co-administered drugs. This study aimed to investigate the metabolism of six 4-substituted analogs of methamphetamine (MA), and their potential inhibition of MA metabolism. The metabolism of MA and the 4-substituted MAs was examined in vitro using human metabolic enzymes. Metabolite analyses were performed using trifluoroacetyl derivatization and GC-MS. The experiments showed that cytochrome P450 2D6 (CYP2D6) was involved in the major metabolic pathway of MA, where it catalyzed N-demethylation of 4-fluoromethamphetamine (4-FMA), 4-chloromethamphetamine (4-CMA), 4-bromomethamphetamine (4-BMA), 4-iodomethamphetamine (4-IMA) and 4-nitromethamphetamine (4-NMA), and O-demethylation of 4-methoxymethamphetamine (4-MMA). The half maximal inhibitory concentration (IC 50 ) values for CYP2D6 using MA as substrate were different for each of the 4-substituted MAs. The strongest inhibitors of amphetamine production from MA were, in order, 4-IMA, 4-BMA, 4-CMA, 4-MMA, 4-FMA, and 4-NMA. The same order was observed for the IC 50 values for inhibition of p-hydroxymethamphetamine production from MA, except for the IC 50 of 4-MMA. The IC 50 values of 4-IMA were lower than the IC 50 values of fluoxetine and higher than that of quinidine. The results of this study imply that the risk of illicit drug interactions fluctuates so widely that unintentional fatal drug poisonings could occur.

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Section: Introductionmentioning

confidence: 99%

Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Taniguchi

Yamamoto²,

Nishi³

2013

AJAC

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“…This proposal is supported by a recent paper which measured the plasma levels of MDEA in a human suffering from an acute toxic response to the drug. Iwersen & Schmoldt (1996) recorded a plasma concentration of MDEA of 96 nmol/ml ante mortem and 216 nmol/ml post mortem. This may be contrasted with plasma concentrations of MDMA of around 10 nmol/ml being recorded in cases of acute toxicity with this drug (Henry et al 1992;Dowling et al 1987).…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence that MDEA has a similar acute toxicity profile to MDMA, there having been reports of MDEA producing hyperthermia, rhabdomyolysis, disseminated intravascular coagulation and liver damage in recreational users (Tsatsakis et al 1997;Gouzoulis-Mayfrank et al 1996;Milroy et al 1996;Sternbach & Varon 1992a & b;Dowling et al 1987;Tehan et al 1993;Iwersen & Schmoldt 1996;Fineschi & Masti 1996). MDEA and MDMA produce similar acute behavioural effects in rats (Paulus & Geyer 1992;Mansbach et al 1989) and there have been several studies which have attempted to compare the relative potency of the 2 drugs in producing long-term neurotoxic degeneration of 5-HT nerve endings in the brain (Schmidt 1987;Stone et al 1987;Ricaurte et ul.…”

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confidence: 99%

The Acute Effect in Rats of 3, 4‐Methylenedioxyethamphetamine (MDEA, “Eve”) on Body Temperature and Long Term Degeneration of 5‐HT Neurones in Brain: A Comparison with MDMA (“Ecstasy”)

Granados

O’Shea

et al. 1999

Pharmacology & Toxicology

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Administration of a single dose of the recreationally used drug 3,4-methylenedioxyethamphetamine (MDEA or "eve") to Dark Agouti rats resulted in an acute dose-dependent hyperthermic response. The peak effect and duration of hyperthermia of a dose of MDEA of 35 mgikg intraperitoneally was similar to a dose of 3,4methylenedioxymetham-phetamine (MDMA or "ecstasy") of 15 mgikg intraperitoneally. Seven days later this dose of M D M A produced a marked (-50%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of ['HI-paroxetine binding in cortex; these losses reflecting the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. In contrast, administration of MDEA (15.25 or 35 mgikg), even at the highest dose, produced only a 20% loss in cortex and hippocampus and no decrease in striatum. The neurotoxic effect of MDEA was only weakly dose-dependent. Neither MDEA (35 mg/kg) nor MDMA (15 mg/kg) altered striatal dopamine content 7 days later. MDEA appeared to have about half the potency of MDMA in inducing acute hyperthermia and 25% of the potency in inducing degeneration of cerebral 5-HT neurones. However since higher doses of MDEA (compared to MDMA) are probably necessary to induce mood changing effects, these data do not support any contention that this compound is a "safer" recreational drug than MDMA in terms of either acute toxicity or long term neurodegeneration.

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“…MDEA has the potential to trigger acute psychotic disorders and induce dysphoric mood, anxiety as well as panic attacks (48,68,70,176). These are the known complications of amphetamines, hallucinogens and cocaine (63,78).…”

Section: Acute Psychiatric Complicationsmentioning

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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Two Very Different Fatal Cases Associated with the Use of Methylenedioxyethylamphet-amine (MDEA): Eve as Deadly as Adam

Cited by 16 publications

References 19 publications

Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

The Acute Effect in Rats of 3, 4‐Methylenedioxyethamphetamine (MDEA, “Eve”) on Body Temperature and Long Term Degeneration of 5‐HT Neurones in Brain: A Comparison with MDMA (“Ecstasy”)

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

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Two Very Different Fatal Cases Associated with the Use of Methylenedioxyethylamphet-amine (MDEA): Eve as Deadly as Adam

Cited by 16 publications

References 19 publications

Comparative &lt;i&gt;in Vitro&lt;/i&gt; Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Comparative &lt;i&gt;in Vitro&lt;/i&gt; Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

The Acute Effect in Rats of 3, 4‐Methylenedioxyethamphetamine (MDEA, “Eve”) on Body Temperature and Long Term Degeneration of 5‐HT Neurones in Brain: A Comparison with MDMA (“Ecstasy”)

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

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Resources

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Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

Comparative <i>in Vitro</i> Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization