A fatal paramethoxymethamphetamine intoxication

Becker, Jürgen C.; Neis, Peter; Röhrich, J.; Zörntlein, Siegfried

doi:10.1016/s1344-6223(02)00096-2

Cited by 33 publications

(20 citation statements)

References 2 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%

“…This creates a compound with similar pharmacological effects, and is performed to circumvent existing drug laws. For example, 4-methoxymethamphetamine (4-MMA) and 4-fluoromethamphetamine (4-FMA), which are 4-substituted psychoactive analogs of methamphetamine (MA), have emerged on the illicit drug market [1,2,[8][9][10][11]. Designer drugs such as illicit amphetamine-type stimulants are often co-administered with other drugs in tablet, capsule, or powder form [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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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

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%

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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“…In addition to MDMA, the amphetamines d-AMP, METH and 4-MTA were selected for this study, due to their widespread presence in ecstasy pills. As amphetamine derivatives are often found as low-level contaminants in street drugs offered as ecstasy (Becker et al 2003), we were also interested in investigating the potential for significant joint effects to occur, even when these individual components were combined at low concentrations, representative of real exposure scenarios. In order to address these questions, three specifically designed mixtures of the same four amphetamines, but combined at three different ratios, were tested.…”

Section: Introductionmentioning

confidence: 99%

The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

2012

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The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

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“…[1][2][3][4][5] Recently, the abuse of their designer drugs including p-methoxyamphetamine (PMA) analogues and 2-methylamino-1-(3,4methy-lenedioxyphenyl)-propan-1-one (methylone) analogues, as shown in Fig. 1, have also been on the rise in Japan as well as in Europe and the U.S.A. [6][7][8][9][10][11][12] More recently, the Japanese authorities, therefore, have begun to prevent not only the recreational uses of the designer drugs under Narcotics and Psychotropics Control Law, but also the importation and distribution under Pharmaceutical Affairs Law.…”

Section: Introductionmentioning

confidence: 99%

Direct Analysis of Conjugate Metabolites of Methamphetamine, 3,4-Methylenedioxymethamphetamine, and Their Designer Drugs in Biological Fluids

Shima

Katagi

Tsuchihashi

2009

JOURNAL OF HEALTH SCIENCE

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This review summarizes technical improvements in the forensic analysis for conjugate metabolites of methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA) and their designer drugs. The improvements include the establishments of liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) in combination with the pretreatment methods. The direct determination techniques for the conjugates proved to be effective in rapidly and accurately examining many biological specimens without annoying hydrolysis. The metabolism of MA and MDMA, with attention to the phase II metabolism of the major hydroxy metabolites, is also discussed based on concentration data in biological specimens obtained from drug abusers.

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A fatal paramethoxymethamphetamine intoxication

Cited by 33 publications

References 2 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 risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

Direct Analysis of Conjugate Metabolites of Methamphetamine, 3,4-Methylenedioxymethamphetamine, and Their Designer Drugs in Biological Fluids

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A fatal paramethoxymethamphetamine intoxication

Cited by 33 publications

References 2 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 risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

Direct Analysis of Conjugate Metabolites of Methamphetamine, 3,4-Methylenedioxymethamphetamine, and Their Designer Drugs in Biological Fluids

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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