MDMA) And 3,4-methylenedioxyamphetamine Research Articles

Cyclic square-wave voltammetric discrimination of the amphetamine-type stimulants MDA and MDMA in real-world forensic samples by 3D-printed carbon electrodes

3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), called as “ecstasy”, are the main seized amphetamine-type stimulants consumed worldwide. Based on the voltammetric profiles of MDMA and MDA on 3D-printed carbon-black integrated polylactide, we propose a cyclic square-wave voltammetric (CSWV) approach to detect and discriminate both molecules in saliva and seized samples. CSWV combines enhanced sensitivity of pulsed techniques and mechanistic insights of cyclic voltammetry and herein we propose cyclic scans from 0.0 to +1.5 V and back to 0.0 V in Britton-Robinson buffer (0.12 mol L−1 pH=6.0). The first scan showed oxidation peaks at around +1.1 V for both MDMA and MDA, however, only MDMA showed a second oxidation peak at +1.35 V (stabilization of a cation radical). The reverse scan displayed a reduction peak only for MDA at around +0.2 V (the oxidation product from MDA is only electroactive in the reverse scan). Thus, MDMA can be selectively detected in the forward scan and MDA in the reverse scan. CSWV provided linear ranges from 5.8 to 35.0 µmol L−1 and 3.1 to 21.8 µmol L−1 (r2>0.99) for MDMA and MDA, respectively. Intra-day precision studies (n=10) showed that potential peaks (RSD<0.8%) and current intensity (RSD<3.8%) for all electrochemical processes are repetitive, with LODs lower than 1.8 µmol L−1. Paracetamol, caffeine, amphetamine, methamphetamine, ephylone, lysergic acid diethylamide and a phenethylamine drug (found in ecstasy-like tablets) did not interfere in the detection of MDMA and MDA. Analysis of seized tablets showed results similar to GC-MS. Spiked saliva samples were analyzed (recovery of 83-106%) after dilution in electrolyte. The combination of CSWV and 3D-printed electrodes (disposable devices easily produced in large scale at reduced cost) is highly promising for selective, fast, simple, low-cost, and on-site screening forensics analyses.

Centrifugal microfluidic devices using low-volume reagent storage and inward fluid displacement for presumptive drug detection

Due to the continued rise in drug abuse, there is a critical need for an enhanced on-site presumptive detection method for identifying the possession of illicit drugs. Presumptive field tests are most commonly colorimetric and are susceptible to various complications arising from manual operation these commercial color kits. Additionally, several different color tests are required for complete unknown sample identification, i.e., a separate test is used for identification of cocaine, methamphetamine, heroin, etc. A microfluidic device that can incorporate the multiple color tests utilized for unknown samples into a single device for cost-effectiveness and increased simplicity, and is amenable to objective analysis techniques, is well-suited to address the current on-site color testing limitations. Unfortunately, many of the validated color tests used for detecting illicit drugs contain harsh chemical reagents that are not compatible with inexpensive microfluidic device substrates, i.e., paper and thermoplastics, limiting microfluidic device developments for this application. Here, we propose a simple fabrication technique for generating custom capillary ampules for containing small volumes of chemical reagents that is compatible with cost-effective, thermoplastic centrifugal microfluidic devices, a platform that has shown to be advantageous for field use. Colorimetric reactions for the detection of methamphetamine, codeine, heroin, cocaine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) were utilized here for proof-of-principle. Additional utility of this reagent storage approach was evaluated for fluid movement towards the center of rotation within centrifugal devices, allowing for more complex sample processing. Inward fluid movement was performed over a radial distance of 50 mm within 3 s.

Detection of phentermine in hair samples from drug suspects

Phentermine (PT) has been widely used as an anti-obesity drug. This drug has to be used with caution due to its close resemblance with amphetamines in its structure and toxicity profile. Recently, PT is in distribution by illegal modes and is found to be available through sources such as the internet, thus their misuse and/or abuse is threatening to be a serious social issue. In the present study, 32 cases of drug suspects were observed for PT abuse, detected using hair samples for drug analysis. PT and other amphetamines, such as methamphetamine (MA), amphetamine (AP), 3,4-methylenedioxyamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), were extracted using 1% HCl in methanol for 20 h at 38°C. The extracts were derivatized with trifluoroacetic anhydride (TFAA) and analyzed using gas chromatography/mass spectrometry (GC/MS). Among the 32 cases of PT abuse, MA and its main metabolite, AP were identified in seven cases and MDMA and its main metabolite, MDA were detected in two other cases.

Detection of 1-Benzylpiperazine, 1-(3-Trifluoromethylphenyl)-piperazine, and 1-(3-Chlorophenyl)-piperazine in 3,4-Methylenedioxymethamphetamine-Positive Urine Samples

Historically, ecstasy tablets contained 3,4-methylenedioxymethamphetamine (MDMA) as the psychoactive component. In recent years, the Drug Enforcement Administration (DEA) and other law enforcement agencies have seized ecstasy tablets that are comprised of psychoactive drugs or drug mixtures other than MDMA. Many jurisdictions have reported the presence of piperazine derivatives including 1-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)-piperazine (TFMPP), and 1-(3-chlorophenyl)-piperazine (mCPP) in ecstasy tablets. These piperazine derivatives produce stimulant and psychoactive effects similar to those produced by MDMA, amphetamine, and methamphetamine. In many countries, their use is not controlled, and therefore they have become a legal alternative to MDMA. For this study, a targeted population of 251 MDMA-positive urine samples were analyzed for designer drugs, including the piperazine derivatives. A basic liquid-liquid extraction followed by pentafluoropropionic anhydride (PFPA) derivatization and a full scan (m/z 42-550) gas chromatography-mass spectrometry analysis was used to screen the urine samples for 33 designer drugs. Overall, in 36% of the specimens analyzed, a stimulant or psychoactive compound other than MDMA and 3,4-methylenedioxyamphetamine (MDA) was detected. BZP, TFMPP, and mCPP were detected in 15%, 7%, and 1% of the samples, respectively.

Metabolism and Urinary Excretion of N-Hydroxy-3,4-methylenedioxymethamphetamine, a Recently Banned Narcotic in Japan

The metabolism and urinary excretion of N-hydroxy-3,4-methylenedioxymethamphetamine (N-OH MDMA), a newly banned narcotic in Japan, were explored to confirm biotransformation of N-OH MDMA to 3,4-methylenedioxymethamphetamine (MDMA) and to discriminate between N-OH MDMA and MDMA intake in forensic urine analysis. The in vitro and the in vivo experiences were performed with human liver S9 and rats, respectively, and the resultant products or metabolites were determined using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. In both the in vitro and the in vivo experiences, MDMA and 3,4-methylenedioxyamphetamine (MDA) were detected, and the MDA levels exceeded the MDMA levels throughout the entire periods except for during 3 h after administration to the rats. This suggests the existence of the metabolic pathway(s) from N-OH MDMA to MDA not via MDMA. In urine samples from the administered rats parent N-OH MDMA and its demethylated metabolite N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) with very low levels during short period after administration (≤6 h) were detected. The ratios of the urinary MDA/MDMA levels for N-OH MDMA-administered rats were higher than those for MDMA-administered rats. In addition, the determination of urinary diastereomers of glucuronidated 4-hydroxy-3-methoxymethamphetamine (HMMA), MDMA metabolite, revealed that the relative peak intensity of l-HMMA-glucuronide to d-HMMA-glucuronide was higher in the case of N-OH MDMA-administration than in the case of MDMA-administration. Detection of MDMA in both the in vitro and the in vivo experiences suggests that N-OH MDMA intake will result in MDMA excretion also in human urine. To discriminate between N-OH MDMA and MDMA intake the following view points would be applicable in urine analysis: 1) detection of N-OH MDMA and/or N-OH MDA, 2) MDA/MDMA ratio, and 3) peak intensities of diastereomeric HMMA-glucuronides.

Determination of 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-Methylenedioxyamphetamine (MDA) in Urine by High Performance Liquid Chromatography

The present study proposes a simple, inexpensive method for the identification and quantification of 3,4-methylenedioxymethamphetamine (MDMA) and its principal metabolite 3,4-methylenedioxyamphetamine (MDA) in samples of human urine utilizing high performance liquid chromatography with a UV detector. The optimized method presented adequate linearity, sensitivity, precision, selectivity, and robustness, thereby demonstrating its feasibility for adoption as a laboratorial option for the confirmation of the presence of the drug in urine samples from users.

Multiple Drug Ingestion by Ecstasy Abusers in the United States

The abuse of ecstasy-type drugs such as 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) is generally associated with young adults attending "Rave" parties. Little toxicological information has been reported regarding ecstasy usage by individuals undergoing monitoring in other settings in the United States. The goal of this study was to determine the prevalence and patterns of licit and illicit drugs in urine specimens of ecstasy users. A survey of laboratory data over the years 2005-2007 revealed that 198 urine specimens were confirmed positive (cutoff concentration 100 ng/mL) for MDMA and/or MDA from the following types of donors ( positive specimens): Correctional (159); Sports (19); Workplace (9); Pain Patients (8); and Special Test Requests (3). Of these, 122 (61.6%) were positive for MDMA and MDA, 70 (35.4%) were positive for MDMA, and 6 (3.0%) were positive for MDA. A majority (84.3%) of the specimens contained multiple drugs and/or metabolites in addition to MDMA and MDA. The median number of drugs/metabolites reported for these ecstasy users was 5 (range, 1-9). In addition to MDMA/MDA, the most commonly identified drug groups (%) were cannabis (THCCOOH) (61.6%); amphetamine/ methamphetamine (38.4%); benzoylecgonine (30.8%); diazepam-related (9.6%); opiates (7.1%); alprazolam (5.6%); and others (5.6%). Although multidrug ingestion appears to be common amongst ecstasy users, caution is recommended in interpretation. Illicit ecstasy in the United States and Canada frequently contains methamphetamine and other active substances, and multidrug use may not have been intentional.

Development of an on-site screening system for amphetamine-type stimulant tablets with a portable attenuated total reflection Fourier transform infrared spectrometer

We tried to develop a library search system using a portable, attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectrometer for on-site identification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) tablets. The library consisted of the spectra from mixtures of controlled drugs (e.g. MDMA and ketamine), adulterants (e.g. caffeine), and diluents (e.g. lactose). In the seven library search algorithms, the derivative correlation coefficient showed the best discriminant capability. This was enhanced by segmentation of the search area. The optimized search algorithm was validated by the positive ( n = 154, e.g. the standard mixtures containing the controlled drug, and the MDMA/MDA tablets confiscated) and negative samples ( n = 56, e.g. medicinal tablets). All validation samples except for four were judged truly. Final criteria for positive identification were decided on the basis of the results of the validation. In conclusion, a portable ATR-FT-IR spectrometer with our library search system would be a useful tool for on-site identification of amphetamine-type stimulant tablets.

Sensitive determination of MDMA and its metabolite MDA in rat blood and brain microdialysates by HPLC with fluorescence detection

Simultaneous determination of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in rat blood and brain microdialysates by high-performance liquid chromatography with fluorescence detection (HPLC-FL) was developed. Microdialysates were directly subjected to derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl). The DIB-derivatives of MDMA, MDA and the internal standard, 1-methyl-3-phenylpropylamine (MPPA), were isocratically separated on an ODS column using a mixture of 50 mm phosphate buffer (pH 7.0)-acetonitrile-methanol-2-propanol (50:45:5:2, v/v/v/v %) as an eluent at a flow rate of 1.5 mL/min. The calibration curves of MDA and MDMA spiked to blood and brain microdialysates were linear over the ranges 2.5-500 and 5.0-1000 ng/mL, respectively. The detection limits of MDA and MDMA were 1.2 and 4.2 for blood and 1.3 and 4.8 ng/mL for brain, respectively. Additionally, the intra- and the inter-assay precisions were lower than 5.6% for the blood and brain microdialysates (n = 4). The proposed method was successfully applied for the monitoring of MDMA and its metabolite MDA in rat blood and brain microdialysates, and the pharmacokinetic parameters of MDMA and MDA in the microdialysates after administration of MDMA (5 mg/kg, i.p.) with or without caffeine (20 mg/kg, i.p.) were evaluated.

MDMA and MDA Concentrations in Antemortem and Postmortem Specimens in Fatalities Following Hospital Admission

Over the last 15 years, numerous deaths involving "Ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) have been reported and described in the literature. In most cases, either antemortem or postmortem concentration data are available. Because of the wide range of results and potential idiosyncratic nature of MDMA toxicity, interpretation of both antemortem and postmortem concentrations is difficult. The possible influence of postmortem redistribution may be an overlooked factor, but existing data involve postmortem concentrations from varying anatomical sites. However, this paper describes for the first time an evaluation of the concentrations of MDMA and 3,4-methylenedioxyamphetamine (MDA) found in five fatalities admitted to hospital where both antemortem and postmortem blood samples were available. Admission MDMA and MDA concentrations ranged between 0.55 and 4.33 mg/L and 0 and 0.10 mg/L, respectively, in antemortem serum/plasma. Postmortem blood MDMA and MDA concentrations ranged between 0.47 and 28.39 mg/L and 0.02 and 1.33 mg/L, respectively. Postmortem concentrations were higher than corresponding antemortem concentrations in all 5 cases with postmortem/antemortem ratios between 1.1 and 6.6 for MDMA and 1.5 and 13.3 for MDA. Differences in concentrations were also observed between anatomical sites, with central sites (e.g., heart) having much higher concentrations than peripheral sites (e.g., femoral). Overall, MDMA and MDA appear to exhibit postmortem redistribution and concentrations measured in postmortem specimens (even from peripheral sites) are not directly comparable with antemortem findings close to or prior to death.

The prevalence of MDMA/MDA in both hair and urine in drug users

The prevalence and age distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in hair samples by gas chromatography/mass spectrometry (GC/MS) were studied. The recoveries obtained from hair were 97% and 99% for MDMA and MDA, respectively. The inter- and intra-assay precision and accuracy were determined. Out of 791 hair samples, 44 (5.6 %) contained MDMA and/or MDA. Out of these 44 subjects, urinalyses from 35 were negative for both MDMA and MDA, while only 9 were positive. We also evaluated concentrations of MDMA and MDA, and the metabolite-to-parent drug ratios. This study showed that the abuse of MDMA or MDA was found principally among young adults and male abusers. We found the epidemiology of ecstasy users in Korea between March 2002 and April 2003.

Post-mortem redistribution of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rabbit. Part I: experimental approach after in vivo intravenous infusion.

Post-mortem redistribution is known to influence blood and tissue levels of various drugs. An animal model was used in an attempt to elucidate this problem for the amphetamine analogue, 3,4-methylenedioxymethamphetamine (MDMA). Rabbits received 1 mg/kg MDMA intravenously (iv) and were killed 2 h later in order to simulate the state of complete distribution in the body. MDMA and 3,4-methylenedioxyamphetamine (MDA) concentrations were determined in blood, urine, bile, vitreous humour, and various tissues (eye globe walls, brain, cardiac muscle, lungs, liver, kidneys, iliopsoas muscle and adipose tissue) using a high pressure liquid chromatographic (HPLC) procedure with fluorescence detection. In the first group (control group, sampling immediately post mortem) considerable MDMA concentrations were found in the brain and both lungs. In addition, our data indicate the elimination of MDMA by hepatic biotransformation and excretion via the bile. When the animals were preserved either 24 or 72 h post mortem (second group), an increase of MDMA and MDA levels in the liver and the eye globe walls was noticed. In the lungs, on the other hand, they tended to decline as a function of increasing post-mortem interval. MDMA levels in cardiac and iliopsoas muscle were fairly comparable and remained stable up to 72 h after death. In the third group, ligation of the large vessels around the heart took place immediately post mortem, but significant differences in blood and tissue MDMA concentrations between rabbits of group 2 and 3 could not be demonstrated. We therefore conclude that post-mortem redistribution of MDMA at the cellular level (viz. by pure diffusion gradient from higher to lower concentrations) is more important than its redistribution via the vascular pathway. Finally, MDA levels were relatively low in all samples, thus indicating that this is not a major metabolite in the rabbit, at least within the first 2 h after administration.

Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma and urine by gas chromatography with nitrogen–phosphorus detection

A gas chromatographic method with nitrogen–phosphorus detection involving a solid–liquid extraction phase was developed and validated for the simultaneous quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in plasma. A modification of this method was validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical conditions described, the limits of detection in plasma and urine were less than 1.6 μg/l and 47 μg/l, respectively, for all the compounds studied. Good linearity was observed in the concentration range evaluated in plasma (5–400 μg/l) and urine (100–2000 μg/l) for all compounds tested. The recoveries obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA. Methods have been successfully used in the assessment of plasma and urine concentrations of MDMA and its main metabolites in samples from clinical studies in healthy volunteers.

Assessment of the MDA and MDMA Optical Isomers in a Stimulant-Hallucinogen Discrimination

The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investigations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have demonstrated that animals trained to discriminate amphetamine from vehicle generalize to the S(+)-isomers but not the R(-)-isomers of MDA and MDMA while animals trained to discriminate LSD from saline generalize to R(-)-MDA and neither isomer of MDMA. However, animals trained to discriminate mescaline from vehicle generalize to both stereoisomers of these phenylisopropylamine derivatives. The present study consisted of two experiments in which a three-choice drug discrimination procedure was employed to compare the stereoisomers of MDA and MDMA to both amphetamine and either mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague–Dawley rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5 mg/kg) and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD (0.08 mg/kg) from saline in three-choice, food reinforced drug discrimination procedures. Substitution tests were administered with the isomers of MDA and MDMA. In the second experiment, substitution tests were also administered with lower doses of each training compound and with the stimulant cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM). In both experiments, all of the isomers produced very few responses on the S(+)-amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA produced nearly complete substitution for mescaline. The results of the second experiment revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and nearly complete substitution with R(-)MDA for LSD. The present findings do not support previous reports that S(+)-MDMA and S(+)-MDA substitute for S(+)-amphetamine. The three-lever drug discrimination procedure may provide a more sensitive behavioral assay in which to examine the discriminative stimulus effects of drugs with compound stimulus properties.

MDA-MDMA concentrations in urine specimens.

Urine specimens collected from active-duty U.S. Army personnel were submitted for analysis to the Tripler Army Medical Center, Forensic Toxicology Drug Testing Laboratory as part of the random drug testing program. During an 18-month drug-screening period, 34 specimens tested positive for amphetamines with the Roche Abuscreen Radioimmunoassay for Methamphetamine (High Specificity); based on gas chromatographic-mass spectrometric (GC-MS) analysis, the presence of 3,4-methylenedioxymethamphetamine (MDMA) was suspected. These samples were subsequently submitted to the Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology for further testing. All 34 samples screened positive using both the Abbott TDx Amphetamine/ Methamphetamine II assay and the Amphetamine class assay. Confirmation and quantitation by GC-MS revealed the presence of both MDMA and 3,4-methylenedioxyamphetamine (MDA) in all samples. The MDMA concentrations ranged from 0.38 to 96.2 mg/L (mean, 13.4 mg/L) and the MDA concentrations ranged from 0.15 to 8.6 mg/L (mean, 1.6 mg/L). The mean ratio of MDA, the N-demethylation metabolite of MDMA, to MDMA was 0.15, similar to the ratio of amphetamine, the N-demethylation metabolite of methamphetamine, to methamphetamine of 0.10. The presence of MDA in urine specimens at a concentration approximately 10-15% that of the MDMA present is consistent with MDMA metabolism, which may be indicative of the use of MDMA only, as compared with the combined use of both drugs.

Microbial transformation of 3,4-methylenedioxy-N-methylamphetamine and 3,4-methylenedioxyamphetamine

The biotransformation of 3,4-methylenedioxy-N-methylarnphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) was examined in the fungus Cunninghamella echinulata. In addition to the reported mammalian metabolites (MDA, 3,4-methylenedioxybenzyl methyl ketoxime, 3,4-methylenedioxybenzyl methyl ketone) and the parent substrate, there were six novel metabolites detected. N-Acetyl-3,4-methylenedioxyamphetamine (NAcMDA) was unequivocally identified and three unidentified metabolites related to NAcMDA were also detected. N-Acetyl-3,4-methylenedioxy-1-phenyl-1-hydroxy-2-aminopropane was tentatively identified as a metabolite of MDMA. The only metabolite of MDA identified was NAcMDA. Two metabolites related to MDA remain unidentified.Key words: Cunninghamella, amphetamine, biotransformation, 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxyamphetamine.

Assessment of the discriminative stimulus effects of the optical isomers of ecstasy (3,4-methylenedioxymethamphetamine; MDMA)

The discriminative stimulus effects of the stereoisomers of 3,4-methylenedioxymethamphetamine (MDMA) were studied in rats trained to discriminate 1.25mg/kg of (+)-MDMA or 3.5mg/kg of (-)-MDMA from saline, in a two lever, water-reinforced, drug discrimination situation. The isomers of MDMA and 3,4-methylenedioxyamphetamine (MDA) substituted completely for both training drugs. The stimulants amphetamine and cocaine did not substitute for either MDMA isomer. The hallucinogens (+/-)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-lysergic acid diethylamide (LSD), and mescaline failed to substitute completely for (+)-MDMA. Similarly, DOM and mescaline did not substitute for (-)-MDMA; however, LSD did substitute for this isomer at a dose of 0.06mg/kg but not at higher doses. Substitution tests with 5-HT-releasing agents revealed that fenfluramine substituted partially for (+)-MDMA and completely for (-)-MDMA, while p-chloroamphetamine substituted completely for both isomers of MDMA. When given in combination with (+)-or (-)-MDMA, neither the 5-HT(2) antagonist pirenpirone nor the less selective 5-HT antagonist metergoline consistently blocked drug-appropriate responding. These results indicate that the stereoisomers of MDMA and MDA have similar discriminative stimulus properties. More importantly, the present findings suggest that 5-HT release may be important for the discriminative stimulus effects of (+)-and (-)-MDMA. Actions at 5-HT(2) receptors, however, do not appear to be critical.

Separation and quantitation of enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) by gas chromatography

Separation and quantitation of enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) by gas chromatography

Stereochemistry of the metabolism of MDMA to MDA

The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA.HCl and blood was obtained by decapitation four hours after dosing. Plasma was separated and extracted. The extract was derivatized on-column with LTPC. In addition to the two MDMA isomers, the demethylated metabolites, S(+) and R(-)-MDA were identified. In all experimental groups (male rats, food deprived male rats, female rats, post partum female rats, and mice) dosed with racemic MDMA, higher levels of the S(+) isomer of MDA relative to the R(-) MDA isomer were observed. This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA.

Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [ 3H]monoamines into synaptosomes from different regions of rat brain

3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [ 3H]monoamines and compared to those of amphetamine and the hallucinogenic phenylisopropylamine 2,5-dimethoxy-4-methylamphetamine (DOM). In contrast to the 5-fold stereoselectivity observed with amphetamine, only the S-(+) enantiomer of MDMA and 3,4-methylenedioxyamphetamine (MDA) inhibited [ 3H]dopamine uptake into striatal synaptosomes. Neither stereoisomer of the α-ethyl homolog of MDMA, N-methyl-l-(l,3-benzodioxol-5-yl)-2-butanamine (MBDB), inhibited [ 3H]dopamine uptake. The two stereoisomers of amphetamine and the MDMA-related compounds were equipotent in inhibiting [ 3H]norepinephrine uptake into hypothalamic synaptosomes. Both steroisomers of MDMA, MDA and MBDB were potent inhibitors of [ 3H]serotonin uptake into hippocampal synaptosomes, but only S-(+)-amphetamine produced an appreciable inhibition of [ 3H]serotonin uptake. Neither steroisomer of DOM inhibited synaptosomal uptake of any [ 3H]monoamine. These results suggest that MDMA and its homologs may be more closely related to amphetamine rather than to DOM in their biochemical mode of action. The pronounced effects of the methylenedioxy-substituted compounds on [ 3H]serotonin and [ 3H]norepinephrine uptake implicate these neurotransmitters in the pharmacological effects of these drugs.