Disease relevance of Methylenedioxymethamphetamine

• In three patients, MDMA or MDEA may have contributed to death by the induction of arrhythmias in individuals with underlying natural disease [1].
• There has been a recent increase in cases of severe toxicity following recreational misuse of small amounts of MDMA [2].
• Hyperpyrexia and rhabdomyolysis after MDMA ("ecstasy") abuse [3].
• In addition, we have monitored 7 cases of hepatotoxicity and suspect that the frequency of this complication is increasing; a history of MDMA misuse should be sought in young people presenting with unexplained jaundice or hepatomegaly [2].
• Oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions [4].

Psychiatry related information on Methylenedioxymethamphetamine

• The widely abused amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, also called "ecstasy") induces hallucination and psychostimulation, as well as long-term neuropsychiatric behaviors such as panic and psychosis [5].
• RESULTS: The MDMA users recalled significantly fewer words than control subjects on delayed (p =.03) but not immediate recall (p =.08) [6].
• METHODS: An auditory verbal memory task (Rey Auditory Verbal Learning Test) was used to study eight abstinent MDMA users and seven control subjects [6].
• MDMA ("ecstasy") and panic disorder: induction by a single dose [7].
• MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion [8].

High impact information on Methylenedioxymethamphetamine

• Some recovery of 5-HT stores can be seen within 24 h of MDMA administration [9].
• In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice [9].
• This review focuses on new insights, obtained from both in vivo and in vitro studies, into the molecular mechanisms whereby amphetamine, and the closely related compounds methamphetamine and methylenedioxymethamphetamine, cause monoamine, and particularly dopamine, release [10].
• This study assessed the neurotoxic potential of MDMA in nonhuman primates [11].
• In addition, MDMA produced pathological changes in nerve cell bodies in the dorsal, but not median, raphe nucleus [11].

Chemical compound and disease context of Methylenedioxymethamphetamine

• Recently, this tenet has been questioned following a study suggesting that MDMA can cause toxicity to dopamine-containing neurons in monkeys [12].
• The MDMA-induced acute 5-HT depletion was prevented by fluoxetine coadministration but the IL-1beta increase and hyperthermia were unaffected [13].
• We examined the effect of a neurotoxic dose of MDMA on IL-1beta concentration and glial activation and their relationship with acute hyperthermia and 5-HT depletion [13].
• Ethanol attenuated the MDMA-induced hyperthermia, but only on the first day [14].
• Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test [15].

Biological context of Methylenedioxymethamphetamine

• Until now, there have been few reports of this type of toxicity from MDMA, which may be related both to the potential of the drug to alter thermoregulation and to the circumstances of misuse [2].
• However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA use on serotonin neurons have not been identified [16].
• We also describe 5 subjects involved in road traffic accidents in whom MDMA was identified [2].
• MEASUREMENTS: Heart rate and blood pressure were measured at regular intervals before and after MDMA administration [4].
• The kinetic parameters of enzymes that regulate the formation of neurotoxic metabolites of MDMA differ among species, as does the ability of MDMA to self-inhibit these enzymes and the degree of genetic polymorphisms exhibited by these enzymes [17].

Anatomical context of Methylenedioxymethamphetamine

• Similarly, the effects of MDMA on neuronal excitability in the nucleus accumbens and in several other brain regions can be prevented by administering drugs that block MDMA-induced 5HT release and can be attenuated by depleting brain DA levels or by administering either DA D1 receptor antagonists or 5HT receptor antagonists [18].
• The effects of methylenedioxymethamphetamine (MDMA, "Ecstasy") on monoaminergic neurotransmission in the central nervous system [18].
• The results establish that MDA and MDMA produce structural damage to 5-HT axon terminals followed by lasting denervation of the forebrain [19].
• Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity [19].
• CONCLUSIONS: Greater decrements in memory function predicted lower NAA/Cr levels-and by inference greater neuronal dysfunction-in the prefrontal cortex of MDMA users [6].

Associations of Methylenedioxymethamphetamine with other chemical compounds

• L-Tryptophan induced a rise in the PRL concentration in controls, but not in MDMA users [20].
• Inotropism, measured by using meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 microg/kg per minute, but did not change after either dose of MDMA [4].
• Amphetamine and substituted amphetamines, including methamphetamine, methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs khat and ephedra, encompass the only widely administered class of drugs that predominantly release neurotransmitter, in this case principally catecholamines, by a non-exocytic mechanism [21].
• Here we demonstrate that subchronic exposure to D-amphetamine, methamphetamine, methylenedioxyamphetamine, and methylenedioxymethamphetamine ('Ecstasy') results in significant neurotoxicity in rat neocortical neurons in vitro [22].
• The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA [23].
• Pretreatment with MDMA or stress alone blunted MDMA-induced 5-HT release in the VTA [24].
• Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge [25].

Gene context of Methylenedioxymethamphetamine

• In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p < .05) [26].
• We have previously shown that MDMA or 5-HT1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT1B receptor-null mice [27].
• We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT1B or 5-HT2C receptors could restore this response [27].
• MDMA metabolism is regulated by the levels of CYP2D6 and COMT (both exhibit some genetic polymorphism), and range of activity of these enzymes may account for some inter-individual differences in terms of toxic responses to the drug [28].
• OBJECTIVES: To clarify whether SERT-selective effects of MDMA at human monoamine transporters can account for the reported MDMA-induced selective toxicity of serotonin neurons in primate brain [29].

Analytical, diagnostic and therapeutic context of Methylenedioxymethamphetamine

• We analysed whether there were differences in 5-HT transporter binding between abstinent MDMA users and participants in the control group [30].
• Positron emission tomography findings in heavy users of MDMA [31].
• OBJECTIVE: To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography [4].
• The indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC), hepatitis C cirrhosis, and cryptogenic cirrhosis [32].
• While individual drugs (i.e., heroin, cocaine, methamphetamine, MDMA) have specific, dose-dependent effects on brain and body temperatures, these effects are strongly modulated by an individual's activity state and environmental conditions, and change dramatically during the development of drug self-administration [33].

References