Disease relevance of 3,4-methylenedioxyamphetamine

• However, when the animals were rendered hypercapnic, CBF was significantly higher in MDA-treated rats than in normal controls, for example, increasing from 356 +/- 22 ml 100 g-1 min-1 in frontal cortex of hypercapnic controls to 700 +/- 81 ml 100 g-1 min-1 in MDA-pretreated rats with similar levels of hypercapnia [1].
• In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone [2].
• The pressor response produced by MDA was accompanied by bradycardia [3].
• All three amphetamine derivatives caused an initial hypothermic response; however, MDA also produced a subsequent hyperthermia, and the speed of recovery from hypothermia was MDA>MDMA>MDEA [3].
• Severe and malignant hyperthermia is a frequently reported factor in emergency department (ED) visits and fatalities in which use of amphetamine drugs, such as (+/-)3,4-methylenedioxymethamphetamine (MDMA), (+/-)3,4-methylenedioxyamphetamine (MDA) and (+)methamphetamine (METH), is confirmed [4].

Psychiatry related information on 3,4-methylenedioxyamphetamine

• 3) S(+)MDMA and (+/-)MDEA produced dose-related increases in the amount of motor activity with minimal changes of the movement patterns in the BPM [5].
• During the course of treatment, two to four (mean, 3.5) administrations of MDA (3,4-methylenedioxyamphetamine) were employed as adjunctive aids in an effort to enhance the psychotherapeutic process [6].
• The authors present two clinical cases, in which psychopathological and cognitive symptoms are detected in MDMA users that support this hypothesis [7].

High impact information on 3,4-methylenedioxyamphetamine

• Via large-scale, random screening of a portion of the receptorome, we have discovered that the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") and its N-demethylated metabolite 3,4-methylenedioxyamphetamine (MDA) each preferentially bind to and activate human recombinant 5-HT2B receptors [8].
• In all animals treated with MDA, there was a significant decrease in serotonin uptake sites throughout the brain, falling from 223 +/- 20 to 40 +/- 16 fmol/mg tissue in parietal cortex, for example, although the raphe nuclei themselves were unaffected (300 +/- 20 fmol/mg tissue in controls and 291 +/- 18 in MDA-treated rats) [1].
• The results suggested that one or more constitutive isoforms (probably unknown) of cytochrome P450 present in rabbit liver microsomes are primarily responsible for MDA demethylenation but that CYP3A6 contributes slightly [9].
• Rats trained to discriminate (+/-) 2,5-dimethoxy-4-methylphenylisopropylamine (DOM) (1.0 mg/kg) from saline, using a standard two-lever operant task, were challenged with various doses of 3,4-methylenedioxyphenylisopropylamine (MDA) and several related agents [10].
• CONCLUSIONS: This gas chromatography-mass spectrometry assay provides adequate sensitivity and performance characteristics for the simultaneous quantification of MDEA, MDMA, and its metabolites HMMA, MDA, and HMA in human urine [11].

Chemical compound and disease context of 3,4-methylenedioxyamphetamine

• Only MDA induced locomotor activity when given alone, but in the presence of BRL 44408, MDMA produced increased locomotor activity [3].

Biological context of 3,4-methylenedioxyamphetamine

• MDEA produced a transient but nonsignificant fall in diastolic pressure [3].
• (+/-)3,4-Methylenedioxyamphetamine elicits action potential bursts in a central snail neuron [12].
• The order of potency for producing isometric contractions of rat aorta (alpha1D) and vas deferens (alpha1A) was MDA>MDMA>MDEA, with MDEA acting as an alpha1-adrenoceptor antagonist with a pK(B) of 4.79+/-0.12 (n = 4) in aorta [3].
• The effects of injection of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyamphetamine (MDEA) (all 20 mg kg(-1)) on blood pressure, heart rate, core body temperature and locomotor activity in conscious rats were investigated using radiotelemetry [3].
• The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype [13].

Anatomical context of 3,4-methylenedioxyamphetamine

• The quantification limits were 0.005 microg/g meconium for amphetamine, methamphetamine, and 4-hydroxy-3-methoxymethamphetamine and 0.004 microg/g meconium for 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine [14].
• We have recently shown that inhibition of brain endothelial cell gamma-glutamyl transpeptidase (gamma-GT) potentiates the neurotoxicity of both MDMA and MDA, indicating that metabolites that are substrates for this enzyme contribute to the neurotoxicity [15].
• The known central nervous system activity of 3,4-methylenedioxyphenylisopropylamine and its N-methyl homolog prompted the synthesis of a series of analogs with substituents on the nitrogen atom [16].
• Therefore, pregnant rats were administered a single dose of MDMA (15 mg/kg, subcutaneous) at embryonic day 14 (E14) and the levels of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were quantified in maternal plasma, amniotic fluid, and fetal brain over 8 h by HPLC [17].
• The behavioral effects of a single, acute dose of methylenedioxyamphetamine (MDA) were assessed using the rabbit nictitating membrane (NM) preparation [18].

Associations of 3,4-methylenedioxyamphetamine with other chemical compounds

• Thus, the objective of the present in vitro study was to evaluate the potential cardiotoxic effects of MDMA and its major metabolites 3,4-methylenedioxyamphetamine (MDA), N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA) using freshly isolated adult rat cardiomyocytes [19].
• The effect of the R(-) and S(+) isomers of 3,4-methylenedioxyamphetamine (MDA) and its N-methyl analog 3,4-methylenedioxymethamphetamine (MDMA) on [3H]inositol monophosphate accumulation was studied in cells expressing either 5-HT2A or 5-HT2C receptors [20].
• Metabolites of 3,4-methylenedioxyamphetamine in the urine of dogs and monkeys were separated by gas-liquid chromatography as their trifluoroacetyl and/or n-butyl ether derivatives and identified by comparison of the chromatographic and mass spectrometric behavior of these derivatives with those of synthetic compounds [21].
• Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE") [22].
• Their concentrations, slightly higher in fingernails than in head hair, were 10.2 and 12.0 ng/mg for AP, 8.0 and 9.7 ng/mg for MDA and 53.4 and 60.2 ng/mg for MDMA in head hair and in fingernails, respectively [23].

Gene context of 3,4-methylenedioxyamphetamine

• The isomers of MDA produced a concentration dependent increase in phosphatidyl inositol (PI) hydrolysis at the 5-HT2A receptors, with the R(-) isomer of MDA being more potent than the S(+) at the 5-HT2A receptor [20].
• The rank order of potency to activate 5HT1C receptors [(-)DOB greater than (+/-) DOI greater than (+)DOB greater than (-)DOM much greater than (-)MDA greater than (+) MDA] was consistent with the rank order of effective behavioral doses in rats and humans [24].
• E. coli beta-glucuronidase hydrolysis MDA recovery was 17.1% and 26.5% greater than acid hydrolysis and H. pomatia beta-glucuronidase recovery (SE = 3.3 and 6.1%), respectively [25].
• Adam and Eve make love. Analysis of the enantiomers of 3,4-methylenedioxy-N-ethylamphetamine (MDE, "Eve") and its metabolite 3,4-methylenedioxyamphetamine (MDA) in rat brain [26].
• Methods for the determination of MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-dihydroxy-methamphetamine (HHMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 3,4-dihydroxyamphetamine (HHA), in biological fluids were established [27].

Analytical, diagnostic and therapeutic context of 3,4-methylenedioxyamphetamine

• METHODS: The enantiomers of MDMA and its demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), present in plasma and urine extracts were derivatized with (-)-(R)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride and analyzed by gas chromatography-mass spectrometry and gas chromatography, respectively [28].
• The enantioselective disposition of MDMA and MDA was determined following oral administration of racemic MDMA (40 mg) to eight male volunteers [28].
• MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days [2].
• A method using high-performance liquid chromatography coupled to ion trap based mass spectrometry (LC/MS) is described for the determination of this compound together with 3,4-methylenedioxymethamphetamine (XTC or MDMA), amphetamine and 3,4-methylenedioxyamphetamine (MDA) in human matrices [29].
• Microdialysis studies on 3,4-methylenedioxyamphetamine and structurally related analogues [30].

References