MDMA as Title Word in search

UI - 16

AU - Barrionuevo M

AU - Aguirre N

AU - Del Rio JD

AU - Lasheras B

AD - Department of Pharmacology, University of Navarra, Pamplona, Spain

TI - Serotonergic deficits and impaired passive-avoidance learning in rats by MDEA: a comparison with MDMA

AB - The serotonergic deficits induced by 3,4-methylenedioxyethamphetamine (MDEA, "eve"), were examined and compared with 3,4 methylenedioxymethamphetamine (MDMA, "ecstasy"). A single dose of MDEA (10, 20, or 40 mg/kg IP) induced a dose-related hyperthermia, but only the highest dose significantly reduced 5-HT content and 5-HT transporter density in the frontal cortex and in the hippocampus 7 days later. Long-term serotonergic deficits were much more marked when MDEA was given repeatedly (40 mg/kg IP., b.i.d., for 4 consecutive days). Single or repeated administration of MDEA induced no change on 5-HT1A receptor density in the frontal cortex, brain stem, or hippocampus, although 3 h after both treatments plasma corticosterone levels were significantly increased. MDEA (5-20 mg/kg, IP) produced significant retention deficits in a passive-avoidance learning task. Conversely, 7 days after the repeated administration of MDEA (40 mg/kg b.i.d., for 4 consecutive days) no effect on passive-avoidance performance was observed unless rats were treated again with another dose of MDEA (20 mg/kg IP) 30 min before the training trial. The 5-HT1A receptor antagonist, WAY 100635, prevented the impairment in retention performance induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH- DPAT), but not by MDEA or MDMA, indicating that the effect of these amphetamine derivates was not mediated by 5-HT1A receptor activation. The results suggest the risk of serotonergic dysfunction associated with MDEA abuse in humans

MH - Animal

MH - Avoidance Learning

MH - drug effects

MH - Carrier Proteins

MH - metabolism

MH - Designer Drugs

MH - pharmacology

MH - Frontal Lobe

MH - Hippocampus

MH - Male

MH - Membrane Glycoproteins

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Paroxetine

MH - Rats

MH - Rats,Wistar

MH - Receptors,Serotonin

MH - Serotonin

MH - Serotonin Agents

MH - Serotonin Uptake Inhibitors

MH - Support,Non-U.S.Gov't

MH - 3,4-Methylenedioxyamphetamine

MH - analogs & derivatives

RP - NOT IN FILE

NT - UI - 20135529LA - EngRN - 0 (serotonin transporter)RN - 0 (Carrier Proteins)RN - 0 (Designer Drugs)RN - 0 (Membrane Glycoproteins)RN - 0 (Receptors, Serotonin)RN - 0 (Serotonin Agents)RN - 0 (Serotonin Uptake Inhibitors)RN - 112692-38-3 (serotonin 1A receptor)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7 (Paroxetine)RN - 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA - 20000314IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 200005

UR - PM:0010672974

SO - Pharmacol Biochem Behav 2000 Feb ;65(2):233-240

UI - 2

AU - Boot BP

AU - McGregor IS

AU - Hall W

AD - Faculty of Medicine, University of Sydney, NSW, Australia

TI - MDMA (Ecstasy) neurotoxicity: assessing and communicating the risks [In Process Citation]

RP - NOT IN FILE

NT - UI - 20290449LA - EngDA - 20000530IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SRO - O:099

UR - PM:0010832852

SO - Lancet 2000 May 20 ;355(9217):1818-1821

UI - 13

AU - Chang L

AU - Grob CS

AU - Ernst T

AU - Itti L

AU - Mishkin FS

AU - Jose-Melchor R

AU - Poland RE

AD - Department of Neurology, UCLA School of Medicine, Harbor-UCLA Medical Center, 1000 W. Carson Street, B-4, Torrance, CA 90509, USA. linda_chang@humc.edu

TI - Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study

AB - 3,4-methylenedioxymethamphetamine (MDMA), an illicit recreational drug, damages serotonergic nerve endings. Since the cerebrovasculature is regulated partly by the serotonergic system, MDMA may affect cerebral blood flow (CBF) in humans. We evaluated 21 abstinent recreational MDMA users and 21 age- and gender-matched healthy subjects with brain SPECT and MRI. Ten of the MDMA subjects also had repeat SPECT and MRI after receiving two doses of MDMA. Abstinent MDMA users showed no significantly different global or regional CBF (rCBF) compared to the control subjects. However, within 3 weeks after MDMA administration, rCBF remained decreased in the visual cortex, the caudate, the superior parietal and dorsolateral frontal regions compared to baseline rCBF. The decreased rCBF tended to be more pronounced in subjects who received the higher dosage of MDMA. Two subjects who were scanned at 2- 3 months after MDMA administration showed increased rather than decreased rCBF. Low-dose recreational MDMA use does not cause detectable persistent rCBF changes in humans. The lack of long-term rCBF changes may be due to a non-significant effect of serotonergic deficits on rCBF, or regeneration of serotonergic nerve terminals. The subacute decrease in rCBF after MDMA administration may be due to the direct effect of MDMA on the serotonergic system or the indirect effects of its metabolites on the dopaminergic system; the preliminary data suggest these effects may be transient

MH - Adult

MH - Brain

MH - drug effects

MH - pathology

MH - radionuclide imaging

MH - Case-Control Studies

MH - Cerebrovascular Circulation

MH - Dose-Response Relationship,Drug

MH - Female

MH - Human

MH - Magnetic Resonance Imaging

MH - Male

MH - Middle Age

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - administration & dosage

MH - adverse effects

MH - Radiopharmaceuticals

MH - diagnostic use

MH - Serotonin Agents

MH - Support,Non-U.S.Gov't

MH - Support,U.S.Gov't,P.H.S.

MH - Technetium Tc 99m Exametazime

MH - Time Factors

MH - Tomography,Emission-Computed,Single-Photon

RP - NOT IN FILE

NT - UI - 20175743LA - EngRN - 0 (Radiopharmaceuticals)RN - 0 (Serotonin Agents)RN - 0 (Technetium Tc 99m Exametazime)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEID - DA00280/DA/NIDAID - MO1 RR00425/RR/NCRRID - MH00534/MH/NIMHDA - 20000509IS - 0165-1781SB - MCY - IRELANDJC - QC4AA - AuthorEM - 200007

UR - PM:0010708923

SO - Psychiatry Res 2000 Feb 28 ;98(1):15-28

UI - 17

AU - de la TR

AU - Farre M

AU - Ortuno J

AU - Mas M

AU - Brenneisen R

AU - Roset PN

AU - Segura J

AU - Cami J

AD - Pharmacology Research Unit, Institut Municipal d'Investigacio Medica (IMIM), Universitat Pompeu Fabra and Universitat Autonoma de Barcelona, Spain. rtorre@imim.es

TI - Non-linear pharmacokinetics of MDMA ('ecstasy') in humans

AB - AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4- hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy- amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity

MH - Adult

MH - Area Under Curve

MH - Blood Pressure

MH - drug effects

MH - Cross-Over Studies

MH - Deoxyepinephrine

MH - analogs & derivatives

MH - urine

MH - Diastole

MH - Dose-Response Relationship,Drug

MH - Double-Blind Method

MH - Hallucinogens

MH - blood

MH - pharmacokinetics

MH - Human

MH - Hydrogen-Ion Concentration

MH - Male

MH - Metabolic Clearance Rate

MH - Methamphetamine

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Pilot Projects

MH - Support,Non-U.S.Gov't

MH - Time Factors

MH - 3,4-Methylenedioxyamphetamine

RP - NOT IN FILE

NT - UI - 20137822LA - EngRN - 0 (Hallucinogens)RN - 117652-28-5 (4-hydroxy-3-methoxymethamphetamine)RN - 15398-87-5 (alpha-methylepinine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 501-15-5 (Deoxyepinephrine)RN - 537-46-2 (Methamphetamine)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 20000302IS - 0306-5251SB - MCY - ENGLANDJC - AU9AA - AuthorEM - 200005

UR - PM:0010671903

SO - Br J Clin Pharmacol 2000 Feb ;49(2):104-109

UI - 6

AU - Erdtmann-Vourliotis M

AU - Mayer P

AU - Riechert U

AU - Hollt V

AD - Institute for Pharmacology and Toxicology, Otto-von-Guericke Universitat, Leipziger Str. 44, 39120, Magdeburg, Germany

TI - Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum [In Process Citation]

AB - Repeated morphine application usually leads to the development of tolerance but under certain circumstances sensitization may arise simultaneously. This phenomenon becomes obvious in behavioral tests as increasing locomotor activity and increasing drug self-administration during a course of chronic morphine application. It was suggested recently that sensitization could contribute to addiction. The molecular mechanisms of sensitization may include the long lasting increase in neuronal responsiveness to morphine which was observed in defined brain areas after repeated morphine injections. In this work, we studied whether morphine-sensitized Wistar rats also display an enhanced neuronal activity in response to other drugs of abuse (so called co-sensitization). The substances to be tested were injected as single doses 4 weeks after completion of a 10-day morphine pretreatment. MDMA (3, 4-methylenedioxymethamphetamine, 6 mg/kg) as a single test dose yielded a c-fos response in a wide range of brain areas. In the caudate putamen, the expression pattern of c-fos was clearly altered if the rats had received repeated morphine application previously. In this case, the MDMA-induced c-fos expression was markedly confined to the centromedial, mesolimbic aspect of the striatum whereas it had a diffuse appearance in rats not exposed to the opiate earlier. Cocaine application (50 mg/kg) elicited an intense c- fos expression in the medial striatum if the animals were morphine- pretreated; it was virtually absent in drug-naive rats after the same cocaine dose. Ten mg/kg cocaine had a similar but weaker effect. No difference in the c-fos expression pattern between morphine and saline pretreated animals was observed in the case of a THC (Delta(9)- tetrahydrocannabinol, 25 mg/kg) or an LSD (lysergic acid diethylamide, 1 mg/kg) test application. These findings imply that morphine sensitizes the brain towards other addicting drugs. In consequence, morphine sensitization obviously does not solely reflect alterations in &mgr;-opioid receptor signaling. Rather, it seems to reflect further rearrangements within the mesolimbic system

RP - NOT IN FILE

NT - UI - 20276033LA - EngDA - 20000617IS - 0169-328XSB - MCY - NETHERLANDSJC - MBRAA - AUTHORRO - O:099

UR - PM:0010814832

SO - Brain Res Mol Brain Res 2000 Apr 14 ;77(1):55-64

UI - 9

AU - Fischer HS

AU - Zernig G

AU - Schatz DS

AU - Humpel C

AU - Saria A

AD - Division of Neurochemistry, Department of Psychiatry, Anichstrasse 35, A-6020 Innsbruck, Austria

TI - MDMA ('ecstasy') enhances basal acetylcholine release in brain slices of the rat striatum [In Process Citation]

AB - The pharmacological basis of acute (+/-)-MDMA (3, 4- methylenedioxymethamphetamine) intoxication still awaits full characterization. According to present knowledge, MDMA enhances the release of serotonin and dopamine in striatal slices and interacts with different types of receptors such as 5-HT2 (5-hydroxytryptamine or serotonin), M1 and M2 muscarinic acetylcholine (ACh), and histamine H1 receptors. Currently, no information is available about the influence of (+/-)-MDMA on striatal cholinergic neurotransmission. In the present study, we used the in vitro perfusion technique to investigate the effect of (+/-)-MDMA on ACh release in rat striatal slices. Perfusions with (+/-)-MDMA (10-300 &mgr;M) resulted in a dose-dependent increase of spontaneous ACh release (EC50 approximately 30 &mgr;M). The effect was reversible and Ca++- and tetrodotoxin-sensitive. To determine the neurochemical pathways underlying this response, we perfused with (+/-)- MDMA in the presence of various inhibitors of neurotransmitter receptors. Blockade of glutamate or muscarinic ACh receptors as well as 5-HT1, 5-HT2, 5-HT3C or dopamine D2 receptors did not modulate (+/-)- MDMA-induced ACh release. However, the presence of histamine H1 receptor antagonists in the perfusion medium abolished (+/-)-MDMA- induced ACh release. The present data clearly demonstrate that (+/-)- MDMA enhances the activity of striatal cholinergic neurons and suggest an involvement of histamine H1 receptors. The effect is not mediated by glutamate and does not involve the activation of receptors of dopamine D2, 5-HT1, 5-HT2, 5-HT3C or muscarinic ACh. Considering the relatively high affinity of (+/-)-MDMA for the H1 histamine receptor (Ki 6 &mgr;M), a direct activation of this type of receptor might represent a plausible mechanism for (+/-)-MDMA-induced ACh release

RP - NOT IN FILE

NT - UI - 20225557LA - EngDA - 20000511IS - 0953-816XSB - MCY - FRANCEJC - BYGAA - AUTHORRO - O:099

UR - PM:0010762366

SO - Eur J Neurosci 2000 Apr ;12(4):1385-1390

UI - 23

AU - Horan B

AU - Gardner EL

AU - Ashby CR

AD - PHS Department, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York 11439, USA

TI - Enhancement of conditioned place preference response to cocaine in rats following subchronic administration of 3, 4- methylenedioxymethamphetamine (MDMA)

AB - In this study, we measured conditioned place preference (CPP) responses to cocaine following subchronic administration of the recreationally abused drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in male Sprague-Dawley rats. Animals were given either vehicle (1 ml/kg of distilled water, s.c.) or MDMA (20 mg/kg, s.c.) twice a day for 4 consecutive days. Two weeks later, CPP responses to cocaine (5, 10, or 20 mg/kg, i.p.) were measured. The MDMA-treated animals showed a significantly greater CPP response to cocaine than the vehicle-treated animals. Since conditioned place preference is believed to be a measure of appetitive behavior, these results suggest that MDMA abuse could lead to an increased vulnerability to the rewarding actions of cocaine and, hence, to increased vulnerability to cocaine addiction and dependence. Copyright 2000 Wiley-Liss, Inc

MH - Animal

MH - Appetite

MH - drug effects

MH - physiology

MH - Choice Behavior

MH - Cocaine

MH - pharmacology

MH - Conditioning,Operant

MH - Dose-Response Relationship,Drug

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Rats

MH - Rats,Sprague-Dawley

MH - Reward

MH - Support,Non-U.S.Gov't

MH - Support,U.S.Gov't,P.H.S.

RP - NOT IN FILE

NT - UI - 20079332LA - EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-36-2 (Cocaine)PT - JOURNAL ARTICLEID - R29MH55155/MH/NIMHDA - 20000217IS - 0887-4476SB - MCY - UNITED STATESJC - VFLAA - AuthorEM - 200004

UR - PM:0010611642

SO - Synapse 2000 Feb ;35(2):160-162

UI - 5

AU - Iravani MM

AU - Asari D

AU - Patel J

AU - Wieczorek WJ

AU - Kruk ZL

AD - Department of Pharmacology, Queen Mary & Westfield College, University of London, UK. m.iravani@kcl.ac.uk

TI - Direct effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphe nucleus slices

AB - We examined the effects of pressure ejected 3, 4- methylenedioxymethamphetamine (MDMA) from a micropipette on direct chemically stimulated release, and on electrically stimulated serotonin (5-HT) or dopamine (DA) release in the caudate putamen (CPu), nucleus accumbens (NAc), substantia nigra pars reticulata (SNr), and the dorsal raphe nucleus (DRN) brain slices of rat, using fast cyclic voltammetry (FCV). MDMA is electroactive, oxidising at +1100 mV. When the anodic input waveform was reduced from +1.4 to +1.0 volt, MDMA was not electroactive. Using this waveform, pressure ejection of MDMA did not release 5-HT or DA in brain slices prepared from any of the nuclei studied. MDMA significantly potentiated electrically stimulated 5-HT release in the SNr and DA release in CPu. In the DRN or in the NAc, MDMA was without effect on peak electrically stimulated 5-HT or DA release. The rates of neurotransmitter uptake, expressed as t(1/2), were in all cases significantly decreased after MDMA. The results indicate that MDMA, unlike (+)amphetamine, is not as a releaser of DA or 5-HT, it is a potent inhibitor of both DA and 5-HT uptake. Copyright 2000 Wiley-Liss, Inc

MH - Amphetamine

MH - pharmacology

MH - Animal

MH - Brain

MH - drug effects

MH - metabolism

MH - Caudate Nucleus

MH - Dopamine

MH - Electric Stimulation

MH - Electrochemistry

MH - In Vitro

MH - Injections,Jet

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Nucleus Accumbens

MH - Raphe Nuclei

MH - Rats

MH - Rats,Wistar

MH - Serotonin

MH - Substantia Nigra

RP - NOT IN FILE

NT - UI - 20280163LA - EngRN - 300-62-9 (Amphetamine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6 (Dopamine)PT - JOURNAL ARTICLEDA - 20000606IS - 0887-4476SB - MCY - UNITED STATESJC - VFLAA - AuthorEM - 200008

UR - PM:0010819905

SO - Synapse 2000 Jun 15 ;36(4):275-285

UI - 19

AU - Jurado C

AU - Gimenez MP

AU - Soriano T

AU - Menendez M

AU - Repetto M

AD - Instituto Nacional de Toxicologia, Sevilla, Spain. quim@sev.inaltox.es

TI - Rapid analysis of amphetamine, methamphetamine, MDA, and MDMA in urine using solid-phase microextraction, direct on-fiber derivatization, and analysis by GC-MS

AB - A rapid, sensitive, and solvent-free procedure for the simultaneous determination of amphetamine, methamphetamine, 3,4- methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine was developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. A headspace vial containing the urine sample, NaOH, NaCl, and amphetamine-d3 as the internal standard was heated at 100 degrees C for 20 min. A polydimethylsiloxane fiber was maintained in the vial headspace for 10 min in order to adsorb the amphetaminic compounds, which were subsequently derivatized by exposing the fiber to trifluoroacetic anhydride for 20 min in the headspace of another vial maintained at 60 degrees C for 20 min. The trifluoroacetyl derivatives were desorbed in the GC injection port for 5 min. Several parameters were considered during the method optimization process. These included a comparison of SPME with or without headspace, the required derivatization procedure, and the influence of temperature on the headspace extraction and derivatization methods. The optimized method was validated for the four compounds tested. Calibration curves showed linearity in the range 50-1000 ng/mL (r = 0.9946-0.9999). Recovery data were 71.89-103.24%. The quantitation limits were 10 ng/mL for amphetamine and methamphetamine and 20 ng/mL for MDA and MDMA. All of these data recommend the applicability of the method for use in the analytical routine of a forensic laboratory

MH - Amphetamine

MH - urine

MH - Comparative Study

MH - Dimethylpolysiloxanes

MH - chemistry

MH - Human

MH - Mass Fragmentography

MH - Methamphetamine

MH - Microchemistry

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Reproducibility of Results

MH - Sensitivity and Specificity

MH - Substance Abuse Detection

MH - methods

MH - Sympathomimetics

MH - Temperature

MH - Time Factors

MH - 3,4-Methylenedioxyamphetamine

RP - NOT IN FILE

NT - UI - 20118724LA - EngRN - 0 (Dimethylpolysiloxanes)RN - 0 (Sympathomimetics)RN - 300-62-9 (Amphetamine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 537-46-2 (Methamphetamine)PT - JOURNAL ARTICLEDA - 20000309IS - 0146-4760SB - MCY - UNITED STATESJC - K4RAA - AuthorEM - 200005

UR - PM:0010654563

SO - J Anal Toxicol 2000 Jan ;24(1):11-16

UI - 10

AU - Liechti ME

AU - Baumann C

AU - Gamma A

AU - Vollenweider FX

AD - Psychiatric University Hospital Zurich. Research Department, P.O. Box 68, CH-8029, Zurich, Switzerland. mliechti@bli.unizh.ch

TI - Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are attenuated by the serotonin uptake inhibitor citalopram

AB - 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo- controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self- confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies

MH - Adult

MH - Amphetamine-Related Disorders

MH - drug therapy

MH - physiopathology

MH - psychology

MH - Brain

MH - drug effects

MH - Citalopram

MH - administration & dosage

MH - Double-Blind Method

MH - Female

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Neuropsychological Tests

MH - Nootropic Agents

MH - Serotonin Uptake Inhibitors

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 20197909LA - EngRN - 0 (Hallucinogens)RN - 0 (Nootropic Agents)RN - 0 (Serotonin Uptake Inhibitors)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 59729-33-8 (Citalopram)PT - CLINICAL TRIALPT - CONTROLLED CLINICAL TRIALPT - JOURNAL ARTICLEDA - 20000509IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM - 200007

UR - PM:0010731626

SO - Neuropsychopharmacology 2000 May ;22(5):513-521

UI - 1

AU - Maldonado E

AU - Navarro JF

AD - Area de Psicobiologia, Facultad de Psicologia, Universidad de Malaga, Spain

TI - Effects of 3,4-methylenedioxy-methamphetamine (MDMA) on anxiety in mice tested in the light-dark box [In Process Citation]

AB - 1. The effects of acute administration of 3,4- methylenedioxymethamphetamine (MDMA; "ecstasy") on anxiety tested in the light/dark box were examined in albino male mice of the OF.1 strain. 2. Animals were evaluated in the light/dark test 30 min after injection of MDMA (1, 8, and 15 mg/kg, i.p) or saline. The following parameters were recorded (for 5 min); (a) number of exploratory rearings in the light and dark sections; (b) number of transitions between the lit and dark areas; (c) time spent in the light and dark areas; (d) latency of the initial movement from the light to the dark area, and (e) locomotor activity in light area. 3. MDMA (8 and 15 mg/kg) produced a significant reduction in exploratory activity (rearings and transitions), without decreasing motility, in comparison with saline-treated mice. However, time spent in lit/dark compartments was not significantly affected by the drug, which could be a consequence of the anti-exploratory properties of MDMA. 4. Overall, the behavioral profile found in the light/dark test indicates an anxiogenic- like activity of MDMA in mice. It is suggested, however, that animal models of anxiety which emphasize a social interaction could be more sensitive to the effects of this substance

RP - NOT IN FILE

NT - UI - 20294482LA - EngDA - 20000601IS - 0278-5846SB - MCY - ENGLANDJC - Q45AA - AUTHORRO - O:099

UR - PM:0010836493

SO - Prog Neuropsychopharmacol Biol Psychiatry 2000 Apr ;24(3):463-472

UI - 11

AU - McGuire P

AD - Section of Neuroimaging, Institute of Psychiatry and GKT School of Medicine, London, UK. p.mcguire@iop.kcl.ac.uk

TI - Long term psychiatric and cognitive effects of MDMA use

AB - Clinical case reports suggest that regular MDMA use can be associated with chronic psychiatric symptoms which persist after the cessation of drug use. Neuropsychological comparisons of regular MDMA users and controls also suggest that MDMA use may lead to memory deficits, with other cognitive processes relatively unaffected. This paper reviews these studies and discusses a number of methodological issues that impact on the interpretation of the findings. Methods for examining the biological effects of MDMA use in man are also outlined. Future research should clarify whether MDMA use has long term psychological effects, and if these are related to changes in central serotonergic function

MH - Chronic Disease

MH - Cognition Disorders

MH - chemically induced

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - Memory Disorders

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Neuropsychology

MH - Psychopathology

MH - Recall

MH - drug effects

MH - Serotonin Agents

RP - NOT IN FILE

NT - UI - 20187900LA - EngRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 20000504IS - 0378-4274SB - MSB - XCY - NETHERLANDSJC - VXNAA - AuthorEM - 200007

UR - PM:0010720725

SO - Toxicol Lett 2000 Mar 15 ;112-113():153-156

UI - 4

AU - Parrott AC

AU - Sisk E

AU - Turner JJ

AD - Department of Psychology, University of East London, E15 4LZ, London, UK

TI - Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users [In Process Citation]

AB - Twelve heavy recreational ecstasy drug users (30-1000 occasions), 16 light ecstasy users (1-20 occasions) and 22 non ecstasy user controls, with group mean ages around 21 years, were compared. Three self-rating questionnaires were completed when drug-free: the SCL-90 (an outpatient psychiatric symptom checklist), the impulsiveness venturesomeness and empathy (IVE) scale; and the uplifts, hassles, stresses and cognitive failures questionnaire. Heavy Ecstasy users reported significantly higher scores than controls on the following SCL-90 factors: paranoid ideation, psychoticism, somatisation, obsessionality, anxiety, hostility, phobic anxiety, altered appetite and restless sleep, together with greater IVE impulsiveness. Light ecstasy users generally produced intermediate scores, with significantly higher scores than controls on two factors and significantly lower scores than heavy ecstasy users on another two. Previous reports have described various psychiatric and psychobiological disorders in recreational ecstasy users, but it is not known how typical they are, being mainly based on individual case studies. This is the first study to describe psychological problems in a non clinical sample of young recreational ecstasy users. However, our ecstasy users were polydrug users, with both groups showing significantly greater usage of amphetamine, LSD and cocaine, than the controls. These other illicit drugs probably contributed to their adverse psychobiological profiles, while there is also the possibility of pre-existing differences between ecstasy users and non users. However, since repeated MDMA can cause serotonergic neurotoxicity in laboratory animals and man, these problems may reflect reduced serotonin activity induced by regular ecstasy use

RP - NOT IN FILE

NT - UI - 20283515LA - EngDA - 20000614IS - 0376-8716SB - MCY - IRELANDJC - EBSAA - AUTHORRO - O:099

UR - PM:0010821995

SO - Drug Alcohol Depend 2000 Jul 1 ;60(1):105-110

UI - 12

AU - Ricaurte GA

AU - McCann UD

AU - Szabo Z

AU - Scheffel U

AD - Department of Neurology, Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Baltimore, MD, USA. ricaurte@jhmi.edu

TI - Toxicodynamics and long-term toxicity of the recreational drug, 3, 4- methylenedioxymethamphetamine (MDMA, 'Ecstasy')

AB - The recreational drug, (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), is a potent serotonin (5-HT) neurotoxin in animals. Whether humans who use MDMA incur 5-HT neural injury is unknown. The present studies utilized positron emission tomography (PET) in conjunction with the 5-HT transporter ligand, [11C]McN-5652 to assess the status of brain 5-HT neurons in human MDMA users. Like nonhuman primates treated with neurotoxic doses of MDMA, humans with a history of MDMA use showed lasting decrements in global brain [11C]McN-5652 binding, with decreases in [11C]McN-5652 binding positively correlated to the extent of previous MDMA use. These results suggest that human MDMA use results in brain 5-HT neurotoxicity

MH - Animal

MH - Brain

MH - drug effects

MH - metabolism

MH - Chromatography,High Pressure Liquid

MH - Female

MH - Human

MH - Isoquinolines

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - blood

MH - pharmacology

MH - toxicity

MH - Neurons

MH - Papio

MH - Serotonin Agents

MH - Serotonin Antagonists

MH - Support,U.S.Gov't,P.H.S.

MH - Tomography,Emission-Computed

RP - NOT IN FILE

NT - UI - 20187898LA - EngRN - 0 (Isoquinolines)RN - 0 (Serotonin Agents)RN - 0 (Serotonin Antagonists)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 96795-90-3 (McN 5652)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID - DA05707/DA/NIDAID - DA06275/DA/NIDADA - 20000504IS - 0378-4274SB - MSB - XCY - NETHERLANDSJC - VXNAA - AuthorEM - 200007

UR - PM:0010720723

SO - Toxicol Lett 2000 Mar 15 ;112-113():143-146

UI - 14

AU - Schroeder B

AU - Brieden S

AD - Department of Ophthalmology, Philipps-University, Germany. schroed2@mailer.uni-marburg.de

TI - Bilateral sixth nerve palsy associated with MDMA ("ecstasy") abuse

AB - PURPOSE:To report the association of methylenedioxymetamphetamine (MDMA, "ecstasy") abuse and bilateral sixth nerve palsy. METHODS: Case report. RESULTS: A 17-year-old male presented with horizontal diplopia in all directions of gaze after having taken MDMA tablets at 5-day to 7- day intervals during a 2-month period. Examination showed bilateral sixth nerve palsy. Ocular motility returned to normal within 5 days without use of MDMA and with no other treatment. CONCLUSION: Methylenedioxymetamphetamine "ecstasy" abuse should be considered in the differential diagnosis in otherwise unexplained sixth nerve palsy

MH - Abducens Nerve Diseases

MH - chemically induced

MH - Adolescence

MH - Case Report

MH - Diplopia

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Substance-Related Disorders

MH - etiology

MH - Visual Fields

RP - NOT IN FILE

NT - UI - 20170775LA - EngRN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 20000404IS - 0002-9394SB - ASB - MCY - UNITED STATESJC - 3OQAA - AuthorEM - 200006

UR - PM:0010704573

SO - Am J Ophthalmol 2000 Mar ;129(3):408-409

UI - 7

AU - Tuchtenhagen F

AU - Daumann J

AU - Norra C

AU - Gobbele R

AU - Becker S

AU - Pelz S

AU - Sass H

AU - Buchner H

AU - Gouzoulis-Mayfrank E

AD - Department of Psychiatry and Psychotherapy, Medical Faculty of the University of Technology, Pauwelsstrasse 30, D-52074, Aachen, Germany

TI - High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users

AB - Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well- recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain

MH - Adolescence

MH - Adult

MH - Analysis of Variance

MH - Brain

MH - drug effects

MH - physiology

MH - Brain Mapping

MH - Evoked Potentials,Auditory

MH - Female

MH - Human

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - adverse effects

MH - Receptors,Serotonin

MH - Serotonin

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 20250716LA - EngRN - 0 (Receptors, Serotonin)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL ARTICLEDA - 20000602IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM - 200008

UR - PM:0010788760

SO - Neuropsychopharmacology 2000 Jun ;22(6):608-617

UI - 3

AU - Wareing M

AU - Fisk JE

AU - Murphy PN

AD - Centre for Studies in the Social Sciences, Edge Hill College of Higher Education, Ormskirk, UK

TI - Working memory deficits in current and previous users of MDMA ('ecstasy') [In Process Citation]

AB - Current and previous users of the drug MDMA ('ecstasy') were tested on measures of central executive functioning, information processing speed, and on self-report measures of arousal and anxiety. The results were compared with those for a control group who did not use MDMA. Relative to the control group, both user groups were found to be impaired in some aspects of central executive functioning. Also, there were significant group differences on the measures of anxiety (users were more anxious) and on arousal (previous users scoring higher on the arousal measure relative to current users). Users processed information as quickly as non-users but less accurately. Some possible mediators of the above group differeces are discussed

RP - NOT IN FILE

NT - UI - 20291984LA - EngDA - 20000530IS - 0007-1269SB - MCY - ENGLANDJC - B1SAA - AUTHORRO - O:099

UR - PM:0010832513

SO - Br J Psychol 2000 May ;91 (Pt 2)():181-188

UI - 22

AU - Aguirre N

AU - Barrionuevo M

AU - Ramirez MJ

AU - Del Rio J

AU - Lasheras B

AD - Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain

TI - Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)- induced neurotoxicity

AB - A single administration of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, i.p.), induced significant hyperthermia in rats and reduced 5- hydroxytryptamine (5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the frontal cortex, striatum and hippocampus by 40-60% 1 week later. MDMA treatment also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant alpha-lipoic acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did not prevent the acute hyperthermia induced by the drug; however, it fully prevented the serotonergic deficits and the changes in the glial response induced by MDMA. These results further support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity

MH - Animal

MH - Antioxidants

MH - pharmacology

MH - Astrocytes

MH - drug effects

MH - metabolism

MH - Binding Sites

MH - Carrier Proteins

MH - Fever

MH - chemically induced

MH - Frontal Lobe

MH - cytology

MH - Glial Fibrillary Acidic Protein

MH - analysis

MH - Hippocampus

MH - Hypothermia

MH - Male

MH - Membrane Glycoproteins

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - antagonists & inhibitors

MH - toxicity

MH - Neostriatum

MH - Neuroprotective Agents

MH - Paroxetine

MH - Pyramidal Cells

MH - Rats

MH - Rats,Wistar

MH - Serotonin

MH - Support,Non-U.S.Gov't

MH - Thioctic Acid

RP - NOT IN FILE

NT - UI - 20084683LA - EngRN - 0 (serotonin transporter)RN - 0 (Antioxidants)RN - 0 (Carrier Proteins)RN - 0 (Glial Fibrillary Acidic Protein)RN - 0 (Membrane Glycoproteins)RN - 0 (Neuroprotective Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7 (Paroxetine)RN - 62-46-4 (Thioctic Acid)PT - JOURNAL ARTICLEDA - 20000119IS - 0959-4965SB - MCY - ENGLANDJC - A6MAA - AuthorEM - 200003

UR - PM:0010619665

SO - Neuroreport 1999 Nov 26 ;10(17):3675-3680

UI - 18

AU - Bailly D

AD - Clinique de la Charite, Centre Hospitalier Regional Universitaire, Lille

TI - [Neuropsychiatric disorders induced by MDMA ("Ecstasy")]

AB - If neurotoxicity of MDMA (ecstasy) is now well documented in animals, it is not the same in humans. MDMA intoxication puts the problem of its possible link with the serotonin syndrome and the neuroleptic malignant syndrome. Neuropathological consequences following MDMA intake have been reported, including hemorrhaging and cerebral infarction, cerebral venous sinus thrombosis, and acute inflammatory CNS disease. However, the physiopathology of these complications remains unclear. In the same way, there have been various reports that have attributed MDMA to precipitating the onset of a wide range of psychiatric disorders including sleep disorders, cognitive disorders, panic attacks, depression, flashbacks, psychosis and severe paranoia. Findings suggest that these psychiatric manifestations might be consequences of MDMA induced brain serotonin neurotoxic lesions. All these data are examined from a critical review of the literature

MH - Cerebral Hemorrhage

MH - chemically induced

MH - Cerebral Veins

MH - drug effects

MH - Dopamine

MH - metabolism

MH - English Abstract

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - Mental Disorders

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Paranasal Sinuses

MH - blood supply

MH - Serotonin Agents

MH - Sleep Disorders

MH - Venous Thrombosis

RP - NOT IN FILE

NT - UI - 20133782LA - FreRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 51-61-6 (Dopamine)PT - JOURNAL ARTICLEDA - 20000317IS - 0013-7006SB - MCY - FRANCEJC - EFBAA - AuthorEM - 200005

UR - PM:0010668603

SO - Encephale 1999 Nov ;25(6):595-602

UI - 31

AU - Chang L

AU - Ernst T

AU - Grob CS

AU - Poland RE

AD - Department of Neurology, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA. Linda_Chang@humc.edu

TI - Cerebral (1)H MRS alterations in recreational 3, 4- methylenedioxymethamphetamine (MDMA, "ecstasy") users

AB - 3,4-methylenedioxymethamphetamine (MDMA) is an illicit drug that has been associated with serotonergic axonal degeneration in animals. This study evaluates neurochemical abnormalities in recreational MDMA users. Twenty-two MDMA users and 37 normal subjects were evaluated with magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) in the mid-frontal, mid-occipital, and parietal brain regions. (1)H MRS showed normal N-acetyl (NA) compounds in all brain regions. The myo-inositol (MI) concentration (+16.3%, P = 0.04) and the MI to creatine (CR) ratio (+14.1%, P = 0. 01) were increased in the parietal white matter of MDMA users. The cumulative lifetime MDMA dose showed significant effects on [MI] in the parietal white matter and the occipital cortex. The normal NA concentration suggests a lack of significant neuronal injury in recreational MDMA users. However, the usage-related increase in MI suggests that exposure to MDMA, even at recreational doses, may cause increased glial content. J. Magn. Reson. Imaging 1999;10:521-526. Copyright 1999 Wiley-Liss, Inc

MH - Adult

MH - Aged

MH - Aged,80 and over

MH - Aspartic Acid

MH - analogs & derivatives

MH - analysis

MH - Brain

MH - drug effects

MH - pathology

MH - Brain Chemistry

MH - Choline

MH - Creatine

MH - Female

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - Inositol

MH - Magnetic Resonance Imaging

MH - Male

MH - Middle Age

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Nuclear Magnetic Resonance

MH - Substance-Related Disorders

MH - metabolism

MH - Support,Non-U.S.Gov't

MH - Support,U.S.Gov't,P.H.S.

RP - NOT IN FILE

NT - UI - 99437942LA - EngRN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 56-84-8 (Aspartic Acid)RN - 57-00-1 (Creatine)RN - 62-49-7 (Choline)RN - 6917-35-7 (Inositol)RN - 997-55-7 (N-acetylaspartate)PT - JOURNAL ARTICLEID - DA00280/DA/NIDAID - MO1 RR00425/RR/NCRRID - MH00534/MH/NIMHDA - 19991115IS - 1053-1807SB - MCY - UNITED STATESJC - BEOAA - AuthorEM - 200001

UR - PM:0010508318

SO - J Magn Reson Imaging 1999 Oct ;10(4):521-526

UI - 38

AU - Colado MI

AU - Granados R

AU - O'Shea E

AU - Esteban B

AU - Green AR

AD - Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain. colado@eucmax.sim.ucm.es

TI - 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")

AB - 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 mg/kg intraperitoneally was similar to a dose of 3,4- methylenedioxymethamphetamine (MDMA or "ecstasy") of 15 mg/kg intraperitoneally. Seven days later this dose of MDMA produced a marked (approximately 50%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-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 mg/kg), 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

MH - Amphetamines

MH - toxicity

MH - Animal

MH - Brain

MH - drug effects

MH - metabolism

MH - Cerebral Cortex

MH - Comparative Study

MH - Dose-Response Relationship,Drug

MH - Fever

MH - chemically induced

MH - Hippocampus

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Nerve Endings

MH - Paroxetine

MH - analysis

MH - Rats

MH - Serotonin

MH - Support,Non-U.S.Gov't

MH - Time Factors

MH - Visual Cortex

MH - 3,4-Methylenedioxyamphetamine

MH - analogs & derivatives

RP - NOT IN FILE

NT - UI - 99328154LA - EngRN - 0 (Amphetamines)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7 (Paroxetine)RN - 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA - 19990901IS - 0901-9928SB - MCY - DENMARKJC - PHTAA - AuthorEM - 199911

UR - PM:0010401727

SO - Pharmacol Toxicol 1999 Jun ;84(6):261-266

UI - 43

AU - Colado MI

AU - Esteban B

AU - O'Shea E

AU - Granados R

AU - Green AR

AD - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain. colado@eucmax.sim.ucm.es

TI - Studies on the neuroprotective effect of pentobarbitone on MDMA-induced neurodegeneration

AB - Administration of a dose of 15 mg/kg of the recreationally used drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") to Dark Agouti rats resulted in an acute hyperthermic response which was followed 7 days later by a marked (approximately 45%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding in cortex. These losses reflect the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. Administration of pentobarbitone (40 mg/kg) concurrently with MDMA produced a significant attenuation of the neurotoxic damage, but also acute hypothermia. When the temperature of the MDMA plus pentobarbitone- treated group was kept elevated to that of the MDMA-treated group by the use of a homeothermic blanket, the neuroprotective effect of pentobarbitone was lost. These data demonstrate that pentobarbitone appears to possess no intrinsic neuroprotective activity and the previously reported activity is due to a hypothermic action of the drug

MH - Animal

MH - Body Temperature

MH - drug effects

MH - Brain

MH - pathology

MH - Gaba

MH - physiology

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - toxicity

MH - Neuroprotective Agents

MH - pharmacology

MH - Paroxetine

MH - metabolism

MH - Pentobarbital

MH - Rats

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 99244074LA - EngRN - 0 (Neuroprotective Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 56-12-2 (GABA)RN - 61869-08-7 (Paroxetine)RN - 76-74-4 (Pentobarbital)PT - JOURNAL ARTICLEDA - 19990610IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199908

UR - PM:0010229068

SO - Psychopharmacology (Berl) 1999 Mar ;142(4):421-425

UI - 44

AU - Colado MI

AU - O'Shea E

AU - Esteban B

AU - Granados R

AU - Green AR

AD - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain. colado@eucmax.sim.ucm.es

TI - In vivo evidence against clomethiazole being neuroprotective against MDMA ('ecstasy')-induced degeneration of rat brain 5-HT nerve terminals by a free radical scavenging mechanism

AB - Clomethiazole is an effective neuroprotective agent against the degeneration of 5-HT neurones that follows administration of 3,4- methylenedioxymethamphetamine (MDMA or 'ecstasy'). Since there is good evidence that free radical formation resulting from auto-oxidation of MDMA metabolites is responsible for the degeneration we have examined whether clomethiazole is a free radical scavenger. MDMA (15 mg/kg i.p.) increased the formation of 2,3- and 2,5-dihydroxybenzoic acids (2,3- DHBA and 2,5-DHBA) from salicylic acid perfused through a microdialysis tube implanted in the hippocampus, indicating increased free radical formation. Clomethiazole (50 mg/kg i.p.) administered 5 min prior and 55 min post MDMA prevented both the acute MDMA-induced hyperthermia and the rise in 2,3- and 2,5-DHBA. However, when the temperature of the MDMA + clomethiazole treated rats was kept elevated to that of the MDMA treated rats with a homeothermic blanket there was no inhibition of the MDMA-induced increase in 2,3-DHBA or 2,5-DHBA. These data suggest firstly that free radical formation is inhibited when the acute MDMA- induced hyperthermia is prevented. Secondly the data further indicate that clomethiazole has no free radical scavenging activity since the drug produces substantial neuroprotection when MDMA + clomethiazole treated rats are kept hyperthermic. This conclusion was strengthened by our observation that clomethiazole is a weak inhibitor (IC50 > 1 mM) of lipid peroxidation in synaptosomes when it had been induced by addition of FeCl2 + ascorbic acid

MH - Animal

MH - Biotransformation

MH - Body Temperature

MH - drug effects

MH - Brain

MH - metabolism

MH - Cerebral Cortex

MH - Chlormethiazole

MH - pharmacology

MH - Corpus Striatum

MH - Free Radical Scavengers

MH - Hippocampus

MH - Hydroxybenzoic Acids

MH - Hydroxyindoleacetic Acid

MH - Kinetics

MH - Male

MH - Microdialysis

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - toxicity

MH - Nerve Degeneration

MH - chemically induced

MH - pathology

MH - prevention & control

MH - Nerve Endings

MH - Neuroprotective Agents

MH - Paroxetine

MH - pharmacokinetics

MH - Rats

MH - Salicylic Acid

MH - Serotonin

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 99233241LA - EngRN - 0 (Free Radical Scavengers)RN - 0 (Hydroxybenzoic Acids)RN - 0 (Neuroprotective Agents)RN - 303-38-8 (2-pyrocatechuic acid)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 490-79-9 (2,5-dihydroxybenzoic acid)RN - 50-67-9 (Serotonin)RN - 533-45-9 (Chlormethiazole)RN - 54-16-0 (Hydroxyindoleacetic Acid)RN - 61869-08-7 (Paroxetine)RN - 69-72-7 (Salicylic Acid)PT - JOURNAL ARTICLEDA - 19990624IS - 0028-3908SB - MCY - ENGLANDJC - NZBAA - AuthorEM - 199908

UR - PM:0010218873

SO - Neuropharmacology 1999 Feb ;38(2):307-314

UI - 51

AU - Colado MI

AU - O'Shea E

AU - Granados R

AU - Esteban B

AU - Martin AB

AU - Green AR

AD - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

TI - Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4- methylenedioxymethamphetamine (MDMA or 'ecstasy') administration

AB - 1. We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. 2. Haloperidol (2 mg kg(-1) i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg(-1) i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA + haloperidol treated rats was kept elevated, this protective effect was marginal. 3. MDMA (15 mg kg(-1)) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg(-1) i.p., plus benserazide, 6.25 mg kg(-1) i.p.) injected 2 h after MDMA (15 mg kg(-1)) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg(-1)) injected before a sub-toxic dose of MDMA (5 mg kg(-1)) failed to induce neurodegeneration. 4. The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3- and 2,5- dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. 5. The neuroprotective drug clomethiazole (50 mg kg(-1) i.p.) did not influence the MDMA-induced increase in extracellular dopamine. 6. These data suggest that previous observations on the protective effect of haloperidol and potentiating effect of L-DOPA on MDMA-induced neurodegeneration may have resulted from effects on MDMA-induced hyperthermia. 7. The increased extracellular dopamine concentration following MDMA may result from effects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than an 'amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings

MH - Animal

MH - Body Temperature

MH - drug effects

MH - Brain

MH - metabolism

MH - Dopamine

MH - physiology

MH - Free Radicals

MH - Haloperidol

MH - pharmacology

MH - Levodopa

MH - Male

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - toxicity

MH - Neurodegenerative Diseases

MH - chemically induced

MH - Paroxetine

MH - Rats

MH - Serotonin

MH - analysis

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 99208114LA - EngRN - 0 (Free Radicals)RN - 0 (Levodopa)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6 (Dopamine)RN - 52-86-8 (Haloperidol)RN - 61869-08-7 (Paroxetine)PT - JOURNAL ARTICLEDA - 19990525IS - 0007-1188SB - MCY - ENGLANDJC - B00AA - AuthorEM - 199907

UR - PM:0010193771

SO - Br J Pharmacol 1999 Feb ;126(4):911-924

UI - 36

AU - Dafters RI

AU - Duffy F

AU - O'Donnell PJ

AU - Bouquet C

AD - Psychology Department, Glasgow University, UK. dick@psy.gla.ac.uk

TI - Level of use of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with EEG power and coherence

AB - RATIONALE: Despite animal studies implicating 3,4- methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. OBJECTIVE: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. METHODS: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject's consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. RESULTS: MDMA use was positively correlated with absolute power in the alpha (8-12 Hz) and beta (12-20 Hz) frequency bands, but not with the delta (1-3 Hz) or theta (4-7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. CONCLUSIONS: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs

MH - Adolescence

MH - Adult

MH - Affect

MH - drug effects

MH - Alpha Rhythm

MH - Cognition

MH - Electroencephalography

MH - Hallucinogens

MH - administration & dosage

MH - adverse effects

MH - pharmacology

MH - Human

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Street Drugs

MH - Substance-Related Disorders

MH - diagnosis

RP - NOT IN FILE

NT - UI - 99372548LA - EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990914IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199911

UR - PM:0010445376

SO - Psychopharmacology (Berl) 1999 Jul ;145(1):82-90

UI - 57

AU - de la TR

AU - Ortuno J

AU - Mas M

AU - Farre M

AU - Segura J

TI - Fatal MDMA intoxication [letter; comment]

MH - Anti-HIV Agents

MH - poisoning

MH - Cytochrome P-450 CYP2D6

MH - metabolism

MH - Drug Interactions

MH - Hallucinogens

MH - pharmacokinetics

MH - Human

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Ritonavir

MH - Support,Non-U.S.Gov't

RP - NOT IN FILE

NT - UI - 99151468LA - EngRN - EC 1.14.99.- (Cytochrome P-450 CYP2D6)RN - 0 (Anti-HIV Agents)RN - 0 (Hallucinogens)RN - 0 (Ritonavir)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - COMMENTPT - LETTERDA - 19990311IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM - 199905RO - M:LC1

UR - PM:0010029010

SO - Lancet 1999 Feb 13 ;353(9152):593

UI - 28

AU - Fineschi V

AU - Centini F

AU - Mazzeo E

AU - Turillazzi E

AD - Unit of Legal Medicine, University of Bari, Italy. vfinesc@tin.it

TI - Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases

AB - Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post- mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response

MH - Adult

MH - Case Report

MH - Disseminated Intravascular Coagulation

MH - chemically induced

MH - pathology

MH - therapy

MH - Fatal Outcome

MH - Forensic Medicine

MH - Hallucinogens

MH - chemistry

MH - poisoning

MH - Human

MH - Male

MH - Mass Fragmentography

MH - Myoglobinuria

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Rhabdomyolysis

MH - 3,4-Methylenedioxyamphetamine

MH - analogs & derivatives

RP - NOT IN FILE

NT - UI - 20003472LA - EngRN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA - 19991130IS - 0379-0738SB - MCY - IRELANDJC - F49AA - AuthorEM - 200002

UR - PM:0010533279

SO - Forensic Sci Int 1999 Sep 30 ;104(1):65-74

UI - 34

AU - Gijsman HJ

AU - Verkes RJ

AU - van Gerven JM

AU - Cohen AF

TI - MDMA study [letter; comment]

MH - Animal

MH - Clinical Trials

MH - standards

MH - Ethics,Medical

MH - Hallucinogens

MH - adverse effects

MH - toxicity

MH - Human

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Neurons

MH - drug effects

MH - metabolism

MH - pathology

MH - Receptors,Serotonin

MH - Serotonin

RP - NOT IN FILE

NT - UI - 99411457LA - EngRN - 0 (Hallucinogens)RN - 0 (Receptors, Serotonin)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - COMMENTPT - LETTERDA - 19991008IS - 0893-133XSB - MCY - UNITED STATESJC - ADQEM - 199912RO - M:LC2

UR - PM:0010481843

SO - Neuropsychopharmacology 1999 Oct ;21(4):597

UI - 15

AU - Gouzoulis-Mayfrank E

AU - Hermle L

AU - Kovar KA

AU - Sass H

TI - [Comment on R. Thomasius, M. Schmolke, D. Kraus: MDMA ("Ecstasy") use-- an overview of psychiatric and medical sequelae (letter; comment)]

MH - Drug Contamination

MH - Hallucinogens

MH - adverse effects

MH - Human

MH - N-Methyl-3,4-methylenedioxyamphetamine

MH - Substance-Related Disorders

MH - diagnosis

RP - NOT IN FILE

NT - UI - 20147377LA - GerRN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - COMMENTPT - LETTERDA - 20000324IS - 0720-4299SB - MCY - GERMANYJC - F67EM - 200006RO - M:CNR

UR - PM:0010683753

SO - Fortschr Neurol Psychiatr 1999 Dec ;67(12):574-576

UI - 29