[Section 5][Section 7]
E is for Ecstasy by Nicholas Saunders
Appendix 4: Bibliography
- Ali, S.F., Scallet, A.C., Holson, R.R., Newport, G.D. and Slikker Jr., W.
Acute Administration of MDMA (Ecstasy): Neurochemical Changes Persist up to
120 Days in Rat Brain. Soc. Neurosci. Abstr. 13 904 (1987).
- Rats were given 40 mg/Kg MDMA twice daily for 4 days. After 120 days, some
regions of the brain (frontal cortex, hippocampus) still had serotonin
depletion. There was fighting behaviour noted between rats during the
dosing and for up to two weeks following it.
- Ali, S.F., Scallet, A.C., Newport, G.D., Lipe, G.W., Holson, R.R. and
Slikker Jr., W. Persistent Neurochemical and Structural Changes in Rat
Brain after Oral Administration of MDMA. Res. Commun. Subst. Abuse 10
- Rats were administered short-term intense levels of MDMA orally, and then
assayed for neurological changes after a period of four months. Changes
were seen in the levels of both serotonin and 5-hydroxyindoleacetic acid,
and neurohistological changes in the brain step were observed.
- Anon. Long-term Effects of "Ecstasy": Study Finds Brain Cell Destruction.
NIDA Notes 2 # 3. p. 7 (1987).
- A short distillation of the present state of MDMA research in relationship
to serotonin neurochemistry is presented.
- Battaglia, G. and De Souza, E.B. Pharmacologic Profile of Amphetamine
Derivatives at Various Brain Recognition Sites: Selective Effects on
Serotonergic Systems. NIDA Research Monograph Series #94 240-258 (1989).
- A review is presented of the affinities for a large number of substituted
amphetamine derivatives for several serotonin receptors. An addition, a
pharmacologic profile of binding affinities of MDMA at a number of
recognition sites is tabulated.
- Battaglia, G., Kuhar, M.J. and De Souza, E.B. MDA and MDMA (Ecstasy)
Interactions with Brain Serotonin Receptors and Uptake Sites: In vitro
Studies. Soc. Neurosciences Abs. 12 336.4 (1986).
- The receptor site uptake of the optical isomers, as well as the racemate,
of both MDA and MDMA were measured by separate, selective labelling with
appropriate radioligands. The relationships between the isomers depended on
whether uptake sites or receptors were involved, and differed at different
locations in the brain.
- Battaglia, G., Sharkey, J., Kuhar, M.J. and De Souza, E.B. Neuroanatomic
Specificity and Time Course of Alterations in Rat Brain Serotoninergic
Pathways Induced by MDMA (3,4- Methylenedioxymethamphetamine): Assessment
Using Quantitative Autoradiography. Synapse 8 249-260 (1991).
- A quantitative measure of the change in serotonin uptake sites as a
consequence of MDMA exposure in rats was determined by the use of radio
labelled Paroxetine. Changes as a function of time were noted in defined
areas of the brain.
- Battaglia, G., Yeh, S.Y. and De Souza, E.B. MDMA-Induced Neurotoxicity:
Parameters of Degeneration and Recovery of Brain Serotonin Neurons.
Pharmacol. Biochem. Behav. 29 269-274 (1988).
- A number of parameters were studied to define the nature of the neurotoxic
effect on serotonin axons and terminals. Both the size and frequency of
drug administration resulted in a dose-dependent response. Regeneration of
these neurons was also time dependent, returning to control levels in 12
months. Pretreatment with a serotonin uptake blocker (Citalopram) prevented
the neurodegenerative effects of MDMA. The rat and guinea-pig brains were
affected, whereas the mouse brain was not.
- Battaglia, G., Yeh, S.Y., O'Hearn, E., Molliver, M.E., Kuhar, M.J. and De
Souza, E.B. 3,4-Methylenedioxymethamphetamine and
3,4-Methylenedioxyamphetamine Destroy Serotonin Terminals in Rat Brain:
Quantification of Neurodegeneration by Measurements of [3H]
Paroxetine-Labelled Serotonin Uptake Sites. J. Pharm. Exptl. Therap. 242
- The effects of repeated administration of MDMA and MDA on the levels of rat
brain monoamines and their metabolites are reported. Only the
serotonin-related systems were found to be affected.
- Battaglia, G., Zaczek, R. and De Souza, E. MDMA Effects in Brain:
Pharmacologic Profile and Evidence of Neurotoxicity from Neurochemical and
Autoradiographic Studies. The Clinical, Pharmacological and
Neurotoxicological Effects of the Drug MDMA. Kluwer, New York. (1990) Ed:
- A series of in vitro and in vivo studies of MDMA in rats has allowed a
thorough mapping of the sites of MDMA-induced neurotoxicity.
- Bird, M.P., Svendsen, C.N., Knapp, C., Hrbek, C.C., Bird, E.D. and
Kornetsky, C. Evidence for Dopaminergic and Not Serotonergic Mediation of
the Threshold Lowering Effects of MDMA on Rewarding Brain Stimulation. Soc.
Neurosci. Abstr. 13, Part 3, p. 1323 (1987) No. 365.13.
- An effort was made to determine the rewarding aspect of MDMA by a
combination of brain electrodes and specific neurotransmitter inhibitors.
It is felt that MDMA reinforcing values may be mediated by the dopamine D2
receptor rather than the serotonin 5-HT2 receptor.
- Callaway, C.W., Nichols, D.E., Paulus, M.P. and Geyer, M.A. Serotonin
Release is Responsible for the Locomotor Hyperactivity in Rats Induced by
Derivatives of Amphetamine Related to MDMA. Serotonin: Molecular Biology,
Receptors and Functional Effects, Birkh=E4user Verlag, Basel. J.R. Fozard and
P.R. Saxena, Eds. (1991).
- In rats MDMA produces locomotor hyperactivity, but the spatial pattern of
locomotion differs qualitatively from the pattern of exploration produced
by other psychostimulants.
- Callaway, C.W., Rempel, N., Peng, R.Y. and Geyer, M.A. Serotonin 5-HT1-Like
Receptors Mediate Hyperactivity in Rats Induced by
3,4-Methylenedioxymethamphetamine. Neuropsychopharm. 7 113-127 (1992).
- This study was designed to evaluate the role of different serotonin (5-HT)
receptor subtypes in mediating the effects of MDMA on a rat's exploration
of a novel environment. This study indicates that S-MDMA produces a
characteristic form of locomotor hyperactivity in rats that depends upon
activation of 5-HT1-like receptors, possibly of the 5-HT1b subtype.
- Champney, T.H. and Matthews, R.T. Pineal Serotonin is Resistant to
Depletion by Serotonergic Neurotoxins in Rats. J. Pineal Res. 11 163-167
- A comparison between MDMA and p-chloroamphetamine (pCA) has been made in
the rat with a view to neurotoxicity. Both compounds reduced serotonin
levels in several brain areas, but neither affected the neurotransmitter
levels in the pineal. This gland does not appear to have the serotonin
re-uptake system that is thought to be necessary for MDMA or pCA induced
- Champney, T.H., Golden, P.T. and Matthews, R.T. Reduction of Hypothalamic
Serotonin Levels after Acute MDMA Administration. Soc. Neurosciences Absts.
12 101.6 (1986).
- Cortical, hypothalamic, and pineal levels of catecholamines, serotonin and
5-HIAA were determined shortly following an acute exposure of rats to each
of several doses of MDMA. Dose-dependent decreases of serotonin and 5-HIAA
were noted in some but not other areas of the brain. The catecholamine
levels were unchanged.
- Commins, D.L., Vosmer, G., Virus, R.M., Woolverton, C.R., Schuster, C.R.
and Seiden, L.S. Biochemical and Histological Evidence that
Methylenedioxmethamphetamine (MDMA) is Toxic to Neurons in Rat Brain. J.
Pharm. Exptl. Therap. 241 338-345 (1987).
- MDMA was administered chronically to rats and guinea pigs , and the
neurotransmitter levels were assayed in several portions of the brain.
These levels were found to be related to dosage, and to the extent of
exposure. Anatomical morbidity is carefully described.
- Defrese, G.D.R. (+/-)-3,4-Methylenedioxymethamphetamine (MDMA): Extending
the Debate Regarding Clinical Implications of its Neurotoxicity.
Unpublished manuscript, Department of Pharmacology, U.C. Davis, (1990).
- An experimental approach is proposed, using experimental animals, to
evaluate the toxicological risks to man that might result from the
reintroduction of MDMA into clinical practice.
- De Souza, E.B. and Battaglia, G. Effects of MDMA and MDA on Brain Serotonin
Neurons: Evidence from Neurochemical and Autoradiographic Studies. NIDA
Research Monograph Series #94 196-222 (1989).
- A series of studies with both MDMA and MDA demonstrate dose-dependent
changes in the brain serotonin neurons, which can blocked by pretreatment
with a serotonin uptake blocker.
- DeSouza, E.B., Battaglia, G., Shu, Y.Y. and Kuhar, M.J. In Vitro and In
Vivo Effects of MDA and MDMA (Ecstasy) on Brain Receptors and Uptake Sites:
Evidence for Selective Neurotoxic Actions on Serotonin Terminals. Amer.
Coll. of Neuropsychopharm. p. 207 (Dec. 8-12, 1986).
- MDA and MDMA both showed a relatively high affinity for both 5-HT2
serotoninergic and alpha-2 adrenergic brain receptors, but low affinities
for 5-HT1, and for the alpha-1 and beta adrenergic receptors, as well as
for dopamine, muscarinic, and opiate receptors. Chronic administration of
either drug decreases the number of 5-HT2 receptors in various brain
- Dornan, W.A., Katz, J.L. and Ricaurte, G.A. The Effects of Repeated
Administration of MDMA on the Expression of Sexual Behaviour in the Male
Rat. Pharmacol. Biochem. Behav. 39 813-816 (1991).
- The repeated s.c administration of MDMA to rats produced a disruption of
copulatory behaviour. These effects disappeared within a week.
- Finnigan, K.T., Ricaurte, G.A., Ritchie, L.D., Irwin, I., Peroutka, S.J.
and Langston, J.W. Orally Administered MDMA Causes a Long-term Depletion of
Serotonin in Rat Brain. Brain Research 447 141-144 (1988).
- The oral and sub-cutaneous routes of MDMA toxicity to rat serotonergic
neurons are studied. Both routes lead to a dose dependent serotonin
- Finnegan, K.T., Skratt, J.J., Irwin, I. and Langston, J.W. The
N-Methyl-D-aspartate (NMDA) Receptor Antagonist, Dextrorphan, Prevents the
Neurotoxic Effects of 3,4-Methylenedioxymethamphetamine (MDMA) in Rats.
Neuroscience Letters 105 300-306 (1990).
- In in vivo rat studies with various levels of MDMA and dextrorphan, the
latter drug, a NMDA antagonist, completely prevented the
serotonin-depleting action of MDMA.
- Gaylor, D.W. and Slikker Jr, W. Risk Assessment for Neurotoxic Effects.
Neurotoxicology 11 211-218 (1990).
- A mathematical basis is presented for the estimation of risk as a function
of dose, with drugs that are neurotoxic. An illustration is given for MDMA,
based on rat and monkey data.
- Gehlert, D.R. and Schmidt, C.J. Acute Administration of
Methylenedioxymethamphetamine (MDMA) Results in a Persistent and Selective
Increase in 5-HT1 Receptor Binding in Rat Brain. Pharmacologist 29 ABS-44
- Acute administration of MDMA in the rat showed an increase in serotonin
binding in 24 hours. This occurred in several parts of the brain.
- Glennon, R.A., Titeler, M., Lyon, R.A. and Youssif, M. MDMA ("Ecstasy"):
Drug Discrimination and Brain Binding Properties. Soc. Neurosciences Abstrac
ts 12 250.11 (1986).
- In rats treated chronically with MDMA (trained to discriminate racemic MDMA
from saline), radioligand binding studies were conducted with both
serotonin and dopamine sites. The Ki values for both 5-HT1 and 5-HT2
receptors were highest for the "S" isomers of MDMA and MDA, with the
racemate lower, and the "R" isomer yet lower. There was no particular
affinity for the dopamine receptors studied.
- Gold, L.H., Hubner, C.B. and Koob, G.F. The Role of Mesolimbic Dopamine in
the Stimulant Action of MDMA. Soc. Neurosci. Abstr., Vol. 13, Part 3, p.
833 (1987) No. 234.13.
- The administration of MDMA to rats may involve (like amphetamine) the
release of dopamine. Test animals with lesions induced by 6-hydroxydopamine
showed less motor activity in response to MDMA than control animals.
- Gold, L.H., Hubner, C.B. and Koob, G.F. A Role for the Mesolimbic Dopamine
System in the Psychostimulant Actions of MDMA. Psychopharmacology 99 40-47
- MDMA was evaluated in rats as a stimulant. Lesions induced with
6-hydroxydopamine modified the amphetamine-like responses seen, suggesting
that the drug's action may involve the presynaptic release of dopamine in
the region of the nucleus accumbens.
- Gollamudi, R., Ali, S.F., Lipe, G., Newport, G., Webb, P., Lopez, M.,
Leakey, J.E.A., Kolta, M. and Slikker Jr., W. Influence of Inducers and
Inhibitors on the Metabolism in vitro and Neurochemical Effects in vivo of
MDMA. Neurotox. 10 455-466 (1989).
- A number of experiments were conducted on rats, with the optical isomers of
MDMA. The metabolic formation of MDA by N-demethylation, in vitro, was
greater for the "S" isomer in the female than the male. This effect was
lost with prior phenobarbital induction, and may be related to P-450
isozymes. In in vivo studies, either isomer appeared to be equally
effective in depleting serotonin, but pretreatment studies suggest that an
active metabolite other than MDA is formed.
- Hanson, G.R., Sonsalla, P., Letter, A., Merchant, K.M., Johnson, M., Bush,
L. and Gibb, J.W. Effects of Amphetamine Analogs on Central Nervous System
Neuropeptide Systems. NIDA Research Monograph Series #94 259-269 (1989).
- The effects of a number of substituted amphetamines on polypeptides
associated with extrapyrimidal structures, have been observed. Both MDA and
MDMA are included, and a discussion is presented of their possible
contribution to both motor and mood changes related to drug-exposure.
- Hashimoto, K. and Goromaru, T. Reduction of [3H] 6-Nitroquipazine-labelled
5-Hydroxytrypatmine Uptake Sites in Rat Brain by
3,4-Methylenedioxymethamphetamine. Fund. Clin. Pharmacol. 4 635-641 (1990).
- The administration of the selective serotonin uptake inhibitor
6-nitroquipazine prevented the MDMA-induced reduction of serotonin and
5-hydroxyindoleacetic acid in rat brain. Tritiated 6-nitroquipazine was
used as a probe for determining the receptor sites that recognized by MDMA.
- Hashimoto, K. and Goromaru, T. Reduction of in vivo Binding of
[3H]Paroxetine in Mouse Brain by 3,4-Methylenedioxymeth-amphetamine.
Neuropharmacol. 29 633-639 (1990)
- Pretreatment of a mouse with MDMA significantly modifies the radioactivity
distribution of tritiated Paroxetine, a potent serotonin re-uptake
inhibitor. The relative decrease of binding to hypothallimus and to
cerebral cortex appears to be dose dependent.
- Hashimoto, K. and Goromaru, T. Study of
3,4-Methylenedioxymethamphetamine-Induced Neurotoxicity in Rat Brain Using
Specific In Vivo Binding of [3H] 6-Nitroquipazine. Res Comm. Subst. Abuse
13 191-201 (1992).
- MDMA-induced neurotoxicity in the rat was studied employing 6-nitoquipazine
binding. This radioligand appears to be well suited for studying
neuropathology and neurochemical changes associated with brain serotonin.
- Hashimoto, K., Maeda, H. and Goromaru, T. Antagonism of
3,4-Methylenedioxymethamphetamine-induced Neurotoxicity in Rat Brain by
1-Piperonylpiperazine. Eur. J. Pharmacol. - Envir. Toxicol. and Pharmacol.
Section, 228 171-174 (1992).
- Several serotonin uptake inhibitors were evaluated for their effects on
MDMA-induced neurotoxicity. 6-Nitroquipazine, Paroxetine and
1-piperonylpiperazine were effective, but the immediate homologue of MDMA
(N,alpha-dimethylpiperonylamine) was not.
- Hekmatpanah, C.R., McKenna, D.J. and Peroutka, S.J. Reserpine does not
Prevent 3,4-Methylenedioxyamphetamine-induced Neurotoxicity in the Rat.
Neuroscience Letters (in press) 1989.
- The administration of reserpine to rats, which reduces the brain monoamine
stores in rats, did not prevent the degeneration of serotoninergic nerve
- Hiramatsu, M. and Cho, A.K. Enantiomeric Differences in the Effects of
3,4-Methylenedioxymethamphetamine on Extracellular Monoamines and
Metabolites in the Striatum of Freely-Moving Rats: An in vivo Microdialysis
Study, Neuropharm. 29 269-275 (1990).
- The effects of para-chloroamphetamine and of the optical isomers of MDMA on
the extracellular levels of the metabolites of dopamine and of serotonin
were determined by dialysis. The level of dopamine was increased, and that
of its metabolites decreased, with p-CPA, (+) MDMA and (-) MDMA showing
decreased potency. The serotonin metabolite 5-HIAA was also decreased, but
there was no difference between the two optical isomers of MDMA in the
production of this effect.
- Hoffman, B.J., Mezey, E. and Brownstein, M.J. Cloning of a Serotonin
Transporter Affected by Antidepressants. Science, 254 579-580 (1991).
- A DNA clone for a serotonin transporter has been isolated. The cell uptake
of the complimentary DNA resembles platelet serotonin uptake, and it is
sensitive to antidepressants, amphetamine derivatives and cocaine. MDMA has
an exceptionally high affinity.
- Insel, T.R., Battaglia, G., Johannessen, J.N., Marra, S. and De Souza, E.B.
3,4-Methylenedioxymethamphetamine ("Ecstasy") Selectively Destroys Brain
Serotonin Terminals in Rhesus Monkeys. J. Pharm. Exptl. Therap. 249 713-720
- In rhesus monkeys, the subacute administration of MDMA decreased both
serotonin and 5-HIAA levels. At high levels there was also a decrease in
the number of serotonin uptake sites (implying serotonin terminal
destruction). There appears to be a considerable specificity as to brain
region where these effects are expressed.
- Johnson, M.P. and Nichols, D.E. Neurotoxin Effects of the Alpha-Ethyl
Homologue of MDMA Following Subacute Administration. Pharmacol. Biochem.
Behav. 33 105-108 (1989).
- MBDB, the alpha-ethyl homologue of MDMA, was compared with MDMA in rats, as
to potential neurotoxicity. There was a similar decrease in the number of
observed serotonin binding sites but, unlike MDMA, there were no
significant decreases in dopamine levels observed.
- Johnson, M.P., and Nichols, D.E. Combined Administration of a
Non-Neurotoxic 3,4-Methylenedioxymethamphetamine Analogue with Amphetamine
Produces Serotonin Neurotoxicity in Rats. Neuropharmacology 30 819-822
- Two drugs have been studied in combination, in the rat. MMAI
(5-methoxy-6-methyl-2-aminoindan) and S-(+)-amphetamine by themselves do
not change any serotonin parameters in the rat. However, in combination,
there was a central serotonin neurotoxicity induced. It appears that
dopamine release plays a critical role in the serotonin neurotoxicity
expression of substituted amphetamine derivatives.
- Johnson, M.P., Conarty, P.F. and Nichols, D.E. [3H]Monoamine Releasing and
Uptake Inhibition Properties of 3,4-Methylenedioxymethamphetamine and
p-Chloroamphetamine Analogues. Eur. J. Pharmacol. 200 9-16 (1991).
- A number of analogues of MDMA and of PCA were studied to determine their
effectiveness in inhibiting the uptake of serotonin into synaptosomes, with
or without pretreatment with reserpine. A valid relationship between the
serotonin neurotoxic potential and the dopamine releasing ability of these
compounds was noted.
- Johnson, M.P., Hoffman, A.J. and Nichols, D.E. Effects of the Enantiomers
of MDA, MDMA, and Related Analogues on [3H]Serotonin and [3H]Dopamine
Release from Superfused Rat Brain Slices. Eur. J. Pharmacol. 132 269-276
- The study of a series of MDA homologues (MDA, MDMA, MBDB) showed a dramatic
dependence between chain length and dopamine release. The longer the chain,
the less the release. It is concluded that dopamine release plays a minor
role in the human activity of these compounds.
- Johnson, M.P., Huang, X. and Nichols, D.E. Serotonin Neurotoxicity in Rats
After Combined Treatment with a Dopaminergic Agent Followed by a
Nonneurotoxic 3,4-Methylenedioxymethamphetamine (MDMA) Analogue. Pharm.
Biochem. Beh. 40 915-922 (1991).
- Further evidence has been found linking dopamine to the long-term
serotonergic neurotoxic effects of certain substituted amphetamines such as
MDMA. Studies were conducted with MDAI (5,6-methylenedioxy-2-aminoindan
(itself with a low neurotoxic liability) with several MAO inhibitors
(clorgyline and deprenyl), with a dopamine uptake inhibitor led to no long
term changes. Pretreatment with a dopamine releaser (S-amphetamine) did
produce changes, however.
- Johnson, M.P., Huang, X., Oberlender, R., Nash, J.F. and Nichols, D.E.
Behavioural, Biochemical and Neurotoxicological Actions of the alpha-Ethyl
Homologue of p-Chloroamphetamine. Eur. J. Pharmacol. 191 1-10 (1990).
- The alpha-ethyl homologue of PCA was studied. The relationship of this
compound (CAB) to PCA is that of the non-dopamine releasing MBDB
(N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine) to MDMA. Although CAB
produces less disruption of the dopamine system, its effects on the
serotonin system is similar to that of PCA.
- Johnson, M., Elayan, I., Hanson, G.R., Foltz, R.L., Gibbs, J.W. and Lim,
H.K. Effects of 3,4-Dihydroxymethamphetamine and
2,4,5-Trihydroxymethamphetamine, Two Metabolites of
3,4-Methylenedioxymethamphetamine, on Central Serotonergic and Dopaminergic
Systems. J. Pharm. Exptl. Therap. 261 447-453 (1992).
- Two metabolites of MDMA have been evaluated as to their contribution to
neurotoxicity. The metabolite, 2,4,5- trihydroxymethamphetamine is toxic to
both serotonin and dopamine nerve terminals, although it does not appear to
explain the neurotoxic effects of MDMA.
- Johnson, M., Hanson, G.R. and Gibb, J.W. Effects of Dopaminergic and
Serotonergic Receptor Blockade on Neurochemical Changes Induced by Acute
Administration of Methamphetamine and 3,4-Methylenedioxymethamphetamine.
Neuropharm. 27 1089-1096 (1988).
- By the use of specific neurorecptor ligands, the mechanisms of acute and
long-term changes in the CNS from methamphetamine and MDMA exposure, have
- Johnson, M., Letter, A.A., Merchant, K., Hanson, G.R. and Gibb, J.W.
Effects of 3,4-Methylenedioxyamphetamine and
3,4-Methylenedioxymethamphetamine Isomers on Central Serotonergic,
Dopaminergic and Nigral Neurotensin Systems of the Rat. J. Pharm. Exptl.
Therap. 244 977-982 (1988).
- The difference of the isomers of MDA and MDMA in their ability to induce
neurotransmitter changes and neurotensin immunoreactivity are reported. In
general, the d-isomers of each were the more potent in affecting
- Johnson, M., Stone, D.M., Bush, L.G., Hanson, G.R. and Gibb, J.W.
Glucocorticoid and 3,4-Methylenedioxymethamphetamine (MDMA)-induced
Neurotoxicity Eur. J. Pharmacol. 161 181 (1989).
- A series of studies of the role of the glucocorticoids in the serotonin
neurotoxicity of MDMA in rats has indicated some involvement in the
- Kalix, P. A Comparison of the Effects of Some Phenethylamines on the
Release of Radioactivity from Isolated Rat Caudate Nucleus Prelabelled with
3H-Dopamine. Arzneim. Forsch. 36 1019-1021 (1986).
- A number of phenethylamines were found to be able to release radioactive
dopamine from prelabelled caudate nuclei. MDMA was not spectacular. The
simplest unsubstituted amphetamine derivatives were the most effective.
- Kalix, P., Yousif, M.Y. and Glennon, R.A. Differential Effects of the
Enantiomers of Methylenedioxymeth-amphetamine (MDMA) on the Release of
Radioactivity from (3H)Dopamine-Prelabeled Rat Striatum. Res. Commun.
Subst. Abuse 9 45-52 (1988).
- The S-isomer of MDMA (the more effective stimulant) is more effective than
the R-isomer in releasing tritiated dopamine from rat striatum. It is about
one sixth the potency of S-methamphetamine.
- Kelland, M.D., Freeman,A.S. and Chiodo, L.A.
(+/-)-3,4-Methylenedioxymethamphetamine- induced Changes in the Basal
Activity and Pharmacological Responsiveness of Nigrostriatal Dopamine
Neurons. Europ. J. Pharmacol. 169 11-21 (1989).
- Studies of acute exposure of rats to MDMA showed an inhibition of the
firing of dopamine neurons, and this effect is diminished following the
depletion of either serotonin or dopamine. MDMA appears to exert direct
functional effects on the nigrostriatal dopamine system.
- Kleven, M.S., Woolverton, W.L. and Seiden, L.S. Evidence that both
Intragastric and Subcutaneous Administration of
Methylenedioxmethamphetamine (MDMA) Produce Serotonin Neurotoxicity in
Rhesus Monkeys. Brain Research 488 121-125 (1989).
- Subacute administration of MDMA to rhesus monkeys by both intragastric and
subcutaneous routes was found to lead to depletion of both serotonin and
5-HIAA in various brain regions. Serotonin uptake sites were depleted
following the oral route but not the subcutaneous route.
- Kopajtic, T., Battaglia, G. and De Souza, E.B. A Pharmacologic Profile of
MDA and MDMA on Brain Receptors and Uptake Sites. Soc. Neurosciences
Abstrts. 12 336.1 (1986).
- Both MDA and MDMA were studied at various brain recognition sites using
radioligand binding techniques. The findings suggest that these drugs may
express their effects at serotonin receptors or uptake sites and/or alpha-2
- Logan, B.J., Laverty, R., Sanderson, W.D. and Yee, Y.B. Differences Between
Rats and Mice in MDMA (Methylenedioxmethamphetamine) Neurotoxicity. Europ.
J. Pharmacol. 152 227-234 (1988).
- A single large administration of MDMA to the rat or the mouse caused only
transient changes in serotonin, norepinephrine and dopamine levels (and
those of their metabolites). Repeated administrations were required to
establish long-lasting changes in the rat; the mouse remained relatively
insensitive. It appears that the both the nature and the degree of
neurotoxicity with MDMA is species-specific.
- Lowe, M.T., Nash Jr., J.F. and Meltzer, H.Y. Selective Reduction of
Striatal Type-II Glucocorticoid Receptors in Rats by
3,4-Methylenedioxymethamphetamine (MDMA). Eur. J. Pharmacol. 163 157-161
- A single large s.c. dose of MDMA to rats reduced, in addition to brain
serotonin and 5-HIAA levels, the glucocorticoid levels in the striatum. No
differences in the corticosterone levels were noted, however, suggesting
that it may not play a role in the receptor reduction.
- Lyon, R.A., Glennon, R.A. and Titeler, M. 3,4-Methylenedioxymethamphetamine
(MDMA): Stereoselective Interactions at Brain 5-HT1 and 5-HT2 Receptors.
Psychopharmacology 88 525-526 (1986).
- The assay of the optical isomers of MDA and MDMA with isolated receptors of
rat brains, suggested that MDMA does not work primarily through direct
interaction with serotonin receptors.
- Millan, M.J. and Colpaert, F.C. Methylenedioxymethamphetamine Induces
Spontaneous Tail-flicks in the Rat via 5-HT1a Receptors. Eur. J. Pharmacol.
193 145-152 (1991).
- MDMA, but not amphetamine, induced dose-dependent tail-flicks in restrained
rats. These effects were blocked by serotonin uptake inhibitors,
implicating these receptors in this response.
- Mokler, D.J., Robinson, S.E. and Rosecrans, J.A. Differential Depletion of
Brain 5-Hydroxytryptamine (5-HT) by (+/-) 3,4-Methylenedioxymethamphetamine
(MDMA). Pharmacologist 29 ABS-273 (1987).
- The sensitivity of specific brain areas for the 5-HT depleting effects of
MDMA may relate to the metabolic activity of 5-HT neurones in that region.
- Mokler, D.J., Robinson, S.E. and Rosecrans, J.A. (+/-)
3,4-Methylenedioxymethamphetamine (MDMA) Produces Long-term Reductions in Brain
5-Hydroxytryptamine in Rats. Eur. J. Pharmacol. 138 265-268 (1987).
- Following chronic administration of MDMA to rats, both serotonin and 5-HIAA
became depleted in the brain. It is suggested that MDMA can function as a
- Mokler, D.J., Robinson, S.E. and Rosecrans, J.A. A Comparison of the
Effects of Repeated Doses of MDMA ("Ecstasy") on Biogenic Amine Levels in
Adult and Neonate Rats. Soc. Neurosci. Abstr. 13No. 251.9 p.905 (1987).
- MDMA was given to both adult and neonate rats in 10-40 mg/Kg doses over
several days. The serotonin levels were decreased and the dopamine levels
were significantly increased.
- Molliver, M.E. Serotonergic Neural Systems: What Their Anatomic
Organization Tells Us about Function. J. Clinical Psychopharm. 7 3S-23S
- A review of the organization of the serotonin nervous system is presented.
The findings associated with the neurotoxic effects of MDMA are used as
instructive tools, and speculation is extended as to the role of these
neurons in the generation of the affective state.
- Molliver, M.E., Mamounas, L.A. and Wilson, M.A. Effects of Neurotoxic
Amphetamines on Serotonergic Neurons: Immunocytochemical Studies. NIDA
Research Monograph Series #94 270-305 (1989).
- A highly detailed cytological mapping of the serotonin related structures
in the rat brain, is presented. An immunocytological study, with
anto-serotonin antibodies, has been made with several substituted
amphetamines, including MDA and MDMA. The axon bodies are severely damaged,
but the raphe cell bodies are spared. Some primate studies are discussed.
- Molliver, M.E., O'Hearn, E., Battaglia, G. and De Souza, E.B. Direct
Intracerebral Administration of MDA and MDMA Does Not Produce Serotonin
Neurotoxicity. Soc. Neurosciences Abstrts. 12 336.3 (1986).
- The microinjection of either MDA or MDMA directly in to the cerebral cortex
resulted in no detectable cytotoxicity. This suggests that the
neurotoxicity of both compounds may be due to some metabolite formed
- Monti, J.A., Beaton, J.M., Benington, F., Morin, R.D. and Christian, S.T.
MDMA and MBDB Potentiate Phorbol Ester-Stimulated Catecholamine Release
from PC-12 Cells. Soc. Neuroscience Abstrt. November 13-18, 1988.
- The "S" isomer of both MDMA and MBDB are potent in stimulating catechol
release from PC-12 cells. The norepinephrin and dopamine release was
increased in the presence of phorbol dibenzoate. It is suggested that this
release may be mediated by protein kinase-C.
- Nader, M.A., Hoffmann, S.M. and Barrett, J.E. Behavioural Effects of (+/-)
3,4-Methylenedioxyamphetamine (MDA) and (+/-)
3,4-Methylenedioxymethamphetamine (MDMA) in the Pigeon: Interactions with
Noradrenergic and Serotoninergic Systems. Psychopharmacology 98 183-188
- MDA, MDMA and MDE. were studied in a conditioned behaviour involving
pigeons. MDA was the most potent of the three drugs. The use of serotonin
and dopamine antagonists suggested that the actions of MDA and MDMA are
mediated by different neurotransmitter systems.
- Nash, J.F. and Yamamoto, B.K. Methamphetamine Neurotoxicity and Striatal
Glutamate Release: Comparison to 3,4-Methylenedioxymethamphet- amine. Brain
Research 581 237-243 (1992).
- The neurotoxicity of methamphetamine and MDMA were compared by measuring
the extracellular concentrations of several compounds by microdialysis in
freely moving rats. The long term dopamine neurotoxicity from repeated
methamphetamine administration is mediated, in part, by a delayed increase
in extracellular glutamate. Repeated MDMA administration, at a dose that
produced a long-term depletion of serotonin, had no effect on glutamate
- Nash, J.F., Meltzer, H.Y. and Gudelsky, G.A. Effect of
3,4-Methylenedioxymethamphetamine on 3,4-Dihydroxyphenylalanine
Accumulation in the Striatum and Nucleus Accumbers, J. Neurochem. 34
- The effect of MDMA on dopamine synthesis in rat brain was estimated by
measuring DOPA accumulation following pretreatment with a decarboxylase
inhibitor. It is suggested that dopamine plays a role in the serotonin
depletion produced by MDMA.
- Nash, J.F., Meltzer, H.Y. and Lowy, M.T. The Effect of Adrenalectomy on
MDMA-Induced Dopamine Release in the Striatum as Measured by in vivo
Microdialysis and Depletion of Serotonin. Res. Commun. Subst. Abuse 13
- The interaction of MDMA and corticosterone in neurotransmitter depletion
was studied in adrenalectomized rats. There does not seem to be any
significant role for corticosterone in the MDMA-induced depletionof
serotonin and 5-hydroxyindoleacetic acid.
- Nichols, D.E., Brewster, W.K., Johnson, M.P., Oberlender, R. and Riggs,
R.M. Nonneurotoxic Tetralin and Indan Analogues of
3,4-Methylenedioxyamphetamine (MDA). J. Med. Chem. 33 703-710 (1990).
- Four cyclic analogues of MDA were synthesized and evaluated
pharmacologically. Two indanes and two tetralins were explored through
discrimination studies relative to MDMA or LSD. They appear not to have
- O'Hearn, E., Battaglia, G., De Souza, E.B., Kuhar, K.J. and Molliver, M.E.
Systemic MDA and MDMA, Psychotropic Substituted Amphetamines, Produce
Serotonin Neurotoxicity. Soc. Neurosciences Abstrts. 12 336.2 (1986).
- Rats exposed chronically to either MDA or MDMA were found, on sacrifice, to
have a reduced number of serotonin axon terminals. This was most evident in
cerebral cortex, thalamus, olfactory bulb and striatum, but also occurred
in other areas. This may be due to the binding of these drugs to the uptake
sites. The serotonin cell bodies and the preterminal axons are spared.
- O'Hearn, E., Battaglia, G., De Souza, E.B., Kuhar, M.J. and Molliver, M.E.
Methylenedioxyamphetamine (MDA) and Methylenedioxymethamphetamine (MDMA)
Cause Selective Ablation of the Serotoninergic Axon Terminals in Forebrain:
Immunocytochemical Evidence for Neurotoxicity. J. Neuroscience 8 2788
- Following chronic administration of MDMA (or separately, MDA) to rats,
there is observed a profound loss of serotoninergic neuron axons throughout
the forebrain. Various regions of the brain are compared as to extent of
damage. The catacholamine counterparts are not affected.
- Pan, H.S. and Wang, R.Y. MDMA: Further Evidence that its Action in the
Medial Prefrontal Cortex is Mediated by the Serotoninergic System. Brain
Res. 539 332-336 (1991).
- The administration of MDMA was found to suppress the firing rates of
certain brain neurons in anaesthetized rats. The (+) isomer, but not the
(-) isomer, mimics the racemate. These effects are blocked by the
pretreatment with a serotonin uptake inhibitor.
- Pan, H.S. and Wang, R.Y. The Action of (+/-)-MDMA on Medial Prefrontal
Cortical Neurons is Mediated Through the Serotoninergic System. Brain
Research 543 56-60 (1991).
- Rats anaesthetized with chloral hydrate were given varying amounts of MDMA
intravenously. Electrodes located in the brain showed decreased neuron
excitement. Studies were extended to include pretreatment with
para-chlorophenylalanine and alpha-methyl-paratyrosine. The action of MDMA
apparently involves some endogenous serotonin release.
- Paris, J.M. and Cunningham, K.A. Lack of Serotonin Neurotoxicity after
Intraraphe Microinjection of (+) 3,4-Methylenedioxymethamphetamine (MDMA).
Brain Res. Bull. 28 115-119 (1991).
- Direct injection of MDMA into the dorsal and the median Raphe nuclei was
followed, in two weeks, by assay for serotonin and catecholamine changes.
No apparent neurotoxicity was found.
- Peroutka, S.J. Relative Insensitivity of Mice to
3,4-Methylenedioxymethamphetamine (MDMA) Neurotoxocity. Res. Commun. Subst.
Abuse 9 193-206 (1988).
- The effects of MDMA were determined in mouse brain serotonin uptake sites
using paroxetine binding as a measure. In distinction with rats, there were
no effects that could be observed at dosages of up to 30 mg/Kg,
administered chronically. These findings confirm that in the mouse, MDMA is
not a neurotoxic agent.
- Pierce, P.A. and Peroutka, S.J. Ring-substituted Amphetamine Interactions
with Neurotransmitter Receptor Binding Sites in Human Cortex. Neuroscience
Lett. 95 208-212 (1988).
- Three psychotropic drugs, MDA, MDMA and MDE, were evaluated as to their
affinities for the DOB binding site, as determined by the displacement of
77Br DOB as the labelled radioligand.
- Piercey, M.F., Lum, J.T. and Palmer, J.R. Effects of MDMA ("ecstasy") on
Firing Rates of Seroronergic, Dopaminergic, and Noradrenergic Neurons in
the Rat. Brain Research 526 203-206 (1990).
- MDMA is effective in the depression of serotonin neurons in the dorsal and
median raphe. Noradrenalin neurons in the locus coeruleus were also
depressed at moderate dosages, but dopamine neurons were unaffected.
- Ricaurte G.A. and McCann, U.D. Neurotoxic Amphetamine Analogues: Effects in
Monkeys and Implications for Humans. Ann. N. Y. Acad. Sci. 648 371-82
- A review is presented of the relationships between several
amphetamine-related compounds (such as amphetamine, methamphetamine and
MDMA) and changes in the neurotransmitter area. The changes seen in rodents
are compared to those observed in non-human primates, and speculation is
made concerning further extrapolation to humans. Research with these
compounds should enhance our understanding of central monoaminergic systems
in normal brain function, and their role in the pathophysiology of
- Ricaurte, G.A., Bryan, G., Strauss, L., Seiden, L. and Schuster, C.
Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve
Terminals. Science 229 986-988 (1985).
- MDA was studied and found to produce long lasting reductions in the level
of serotonin, the number of serotonin uptake sites, and the concentration
of 5-HIAA in the rat brain. It was suggested that these deficits were due
to serotonin nerve terminal degeneration. This was the research report that
had been submitted for publication at the time of the MDMA hearings, and
that played a focal role in the emergency scheduling of MDMA.
- Ricaurte, G.A., DeLanney, L.E., Irwin, I. and Langston, J.W. Toxic Effects
of MDMA on Central Serotonergic Neurons in the Primate: Importance of Route
and Frequency of Drug Application. Brain Research 446 165-169 (1988).
- The toxicity of MDMA was studied in primates both by the oral and the
subcutaneous routes, and in single and multiple doses. Multiple doses are
more effective that single doses in depleting serotonin, and the s.c route
is more effective than the oral route. However, a single, oral
administration of MDMA still produces a long-lived depletion
- Ricaurte, G.A., DeLanney, L.E., Wiener, S.G., Irwin, I. and Langston, J.W.
5-Hydroxyindoleacetic acid in Cerebrospinal Fluid Reflects Serotonergic
Damage Induced by 3,4-Methylenedioxymethamphetamine in CNS of Non-human
Primates. Brain Research 474 359-363 (1988).
- The usefulness of 5-hydroxyindoleacetic acid in CSF as a marker for
serotonergic damage induced by MDMA was evaluated in the monkey. Following
toxic doses of MDMA, there was removal of CSF for the assay of this
serotonin metabolite, followed by sacrifice of the animal for direct brain
measurement. The resulting positive correlation supports this technique for
the eventual search for MDMA-induced damage in humans.
- Ricaurte, G.A., Finnegan, K.F., Nichols, D.E., DeLanney, L.E., Irwin, I.
and Langston, J.W. 3,4-Methylenedioxymeth-amphetamine (MDE), a Novel
Analogue of MDMA, Produces Long-lasting Depletion of Serotonin in the Rat
Brain. Eur. J. Pharmacol. 137 265-268 (1987).
- MDE was qualitatively similar to MDMA in the depletion of serotonin in rat
brain, but was only one fourth as potent.
- Ricaurte, G.A., Forno, L.S., Wilson, M.A., DeLanney, L.E., Irwin, I.,
Molliver, M.E. and Langston, J.W. (+/-) Methylenedioxymethamphetamine
(MDMA) Exerts Toxic Effects on Central Serotonergic Neurons in Primates.
Soc. Neurosci. Abstr. 13 No. 251.8 p. 905 (1987).
- MDMA was given s.q. twice daily for four days to monkeys, at 2.5, 3.75 and
5 mg/Kg. Post-mortem brain analyses showed serotonin reduction (90%) and
axon damage. Some was described as "striking" and involved morphological
- Ricaurte, G.A., Forno, L.S., Wilson, M.A., DeLanney, L.E., Irwin, I.,
Moliver, M.E. and Langston, J.W. (+/-) 3,4-Methylenedioxymethamphetamine
Selectively Damages Central Serotonergic Neurons in Nonhuman Primates. J.
Am. Med. Assn. 260 51-55 (1988).
- The parenteral administration (subcutaneous, twice daily for four days) of
MDMA to monkeys of three species produced both brain serotonin depletion
and accompanying neuron damage upon autopsy following a two-week waiting
period. Considerable microscopic detail is given. The evidence presented
could imply, but does not established, that there may be actual neuron cell
death. The humanpattern of use is oral rather than parenteral, but a
warning for prudence is advanced for the human use of either MDMA or (the
neurotoxicologically similar drug) Fenfluramine.
- Ricaurte, G.A., Marletto, A.L., Katz, J.L. and Marletto, M.B. Lasting
Effects of (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) on Ventral
Serotonergic Neurons in Nonhuman Primates: Neurochemical Observations. J.
Pharm. Exptl. Therap. 261 616-622 (1992).
- A study was made of the duration of the neurotoxic effects of MDMA on
squirrel monkeys (5 mg/day, twice daily, for 4 days) as a function of time,
from 2 weeks to a year and a half. A control blank was used. Serotonin
deficits persisted, suggesting that MDMA produces lasting effects.
- Scallet, A.C., Ali, S.F., Holson, R.R., Lipe, G.W. and Slikker Jr., W.
Neurohistological Effects 120 Days after Oral Ecstasy (MDMA): Multiple
Antigen Immunohistochemistry and Silver Degeneration Staining. Soc.
Neurosci. Abstr. 13, Part 3 No. 251.6, p. 904 (1987).
- Both silver degeneration procedures (Fink-Heimer) and immunohistochemical
techniques have been applied to MDMA-treated rats long after dosing. There
are indications of regional differences in recovery, and that some changes
may be irreversible.
- Scheffel, U. and Ricaurte, G.A., Paroxetine as an in vivo Indicator of
3,4-Methylenedioxymethamphetamine Neurotoxicity: A Presynaptic Serotonergic
Positron Emission Tomography Ligand? Brain Research 527 89-95 (1990).
- The value of Paroxetine as an indicator of serotonergic nerve axon damage
was demonstrated by the effectiveness of 5,7-dihydroxytryptamine in
decreasing specific binding. MDMA treatment of rats gave similar reduction
in labelled Paroxetine binding.
- Scheffel, U., Lever, J.R., Stathis, M., Ricaurte, G.A. Repeated
Administration of MDMA Causes Transient Down-regulation of Serotonin 5-HT2
Receptors. Neuropharm. 31 881-893 (1992).
- The repeated administration of MDMA to rats causes a down regulation of
serotonin receptors ion the brain of the rat. N-methyl-2-iodolysergic acid
diethylamide is a suitable ligand for the labelling of these receptors in
vitro and in vivo..
- Schlechter, M.D. Serotonergic-Dopaminergic Mediation of
3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"). Pharmacol. Biochem.
and Behav. 31 817-824 (1989).
- The discriminative stimuli properties of MDMA in rats, were studied to
explore the serotinergic, as contrasted to the dopaminergic, nature of the
drug's action. In the early part of the behavioural responses, the effects
appear to be exclusively serotinergic, but in the latter period, there are
some believable dominergic actions.
- Schmidt, C.J. Acute Administration of Methylenedioxymethamphetamine:
Comparison with the Neurochemical Effects of its N-Desmethyl and N-Ethyl
Analogs. Eur. J. Pharmacol. 136 81-88 (1987).
- MDMA (and its two immediate homologues, MDMA and MDE) were studied in the
serotoninergic systems in the rat brain. There was depletion of cortical
serotonin which in the case of MDMA appeared to persist after at least a
- Schmidt, C.J. Neurotoxicity of the Psychedelic Amphetamine,
Methylenedioxymethamphetamine. J. Pharm. Exptl. Therap. 240 1-7 (1987).
- Evidence is presented that MDMA has a complex effect on rat serotonergic
neurons, that results in a neurotoxic change at the nerve terminals. A
parallel is drawn to the neurotoxin para-chloroamphetamine.
- Schmidt, C.J., Acute and Long-term Neurochemical Effects of
Methylenedioxmethamphetamine in the Rat. NIDA Research Monograph Series #94
- An analysis of short and long-term brain serotonin-related changes was
made, and interpreted. Comparisons were made to PCA, methamphetamine and
- Schmidt, C.J. and Kehne, J.H. Neurotoxicity of MDMA: Neurochemical Effects.
Ann. N. Y. Acad. Sci. 600 665-681 (1990).
- A review of the experimental findings involving both serotonin and dopamine
in the neurotoxic action of MDMA. The actual mechanism of action remains
- Schmidt, C.J. and Lovenberg, W. (+/-)Methylenedioxymethamphetamine (MDMA):
A Potentially Neurotoxic Amphetamine Analogue. Fed. Proc. 45 1059 (#5264)
April 13-18, (1986). Note paper below, Schmidt et al., with this same
- Rats were administered MDMA s.c. at various doses and sacrificed at three
hours. Brain concentrations of dopamine and serotonin, and their major
metabolites were determined. The serotonin concentrations were reduced in a
dose-dependent manner. Co-administration of a serotonin uptake inhibitor,
Citalopram, blocked the MDMA-induced decline in striatal serotonin
concentrations suggesting a mechanism similar to that of the known
serotonergic neurotoxin p-chloroamphetamine.
- Schmidt, C.J. and Lovenberg, W. Further Studies on the Neurochemical
Effects of 4,5-Methylenedioxymethamphetamine and Related Analogues. Soc.
Neurosciences Abstrts. 12 169.5 (1986).
- The racemate and optical isomers of MDMA produced depletion of cortical and
striatal serotonin. The (+) isomer was the more effective material. MDA was
similar to MDMA, but effects produced by the N-ethyl homologue (MDE) were
reversed in a week. Whereas all three drugs caused an acute decrease in
serotonin concentration, only MDA and MDMA reduced the uptake of tritiated
serotonin at the dosages studied (20 mg/Kg).
- Schmidt, C.J. and Taylor, V.L. Direct Central Effects of Acute
Methylenedioxymethamphetamine on Serotonergic Neurons. Eur. J. Pharmacol.
156 121-131 (1988).
- The optical isomers of MDMA were studied separately in the rat as to their
effects on loss of brain tryptophan hydroxylase. This appeared to precede
the drop of serotonin concentration in the same areas. Injections of MDMA
directly into the brain had no effect on either measure.
- Schmidt, C.J. and Taylor, V.L. Neurochemical Effects of
Methylenedioxymethamphetamine in the Rat: Acute versus Long-term Changes.
The Clinical, Pharmacological and Neurotoxicological Effects of the Drug
MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka
- A study is presented describing the changes in the brains of rats which had
been administered MDMA. It is felt that the release of dopamine is a
prerequisite for the neurotoxic effects seen.
- Schmidt, C.J., Abbate, G.M., Black, C.K. and Taylor, V.L. Selective
5-Hydroxytryptamine-2 Receptor Antagonists Protect against the
Neurotoxicity of Methylendioxymethamphetamine in Rats. J. Pharm. Exptl.
Therap. 255 478-483 (1990).
- The characteristic serotonin deficits produced in rats by MDMA were
prevented by the simultaneous administration of serotonin antagonists such
as Ritanserin. The action of such drugs may involve dopamine.
- Schmidt, C.J., Black, C.K., Abbate, G.M. and Taylor, V.L.
Methylenedioxymethamphetamine-induced Hyperthermia and Neurotoxicity are
Independently Mediated by 5-HT2 Receptors. Brain Research 529 85-90 (1990).
- In rats, MDMA produces a hyperthermia which can be partially antagonised,
as can the induced neurotoxicity, by the administration of a serotonin
- Schmidt, C.J., Black, C.K., Abbate, G.M. and Taylor, V.L Chloral Hydrate
Anesthesia Antagonizes the Neurotoxicity of
3,4-Methylenedioxymethamphetamine. Eur. J. Pharmacol. 191 213-216 (1990).
- When chloral anesthesia is administered to rats that have been administered
MDMA, there is an interference with the induced neurotoxicity. This may be
due to some role played by dopamine release.
- Schmidt, C.J., Black, C.K. and Taylor, V.L. Antagonism of the Neurotoxicity
due to a Single Administration of Methylenedioxyamphetamine. Eur. J.
Pharmacol. 181 59-70 (1990).
- A complex series of experiments in the rat investigating MDMA has suggested
that the release of both dopamine and serotonin are implicated in the
observed neurotoxicity of MDMA.
- Schmidt, C.J., Black, C.K. and Taylor, V.L. L-DOPA Potentiation of the
Serotoninergic Deficits Due to a Single Administration of
3,4-Methylenedioxymethamphetamine, p-Chloroamphetamine or Methamphetamine
to Rats. Eur. J. Pharmacol. 203 41-49 (1991).
- The role of dopamine in the serotoninergic neurotoxicity of MDMA, PCA,
methamphetamine, MDE, and Fenfluramine was assessed by their
co-administration with L-DOPA. The findings reported support a role for
dopamine release in the toxicity of the first three of these drugs.
- Schmidt,C.J., Levin, J.A. and Loverberg, W. In Vitro and In Vivo
Neurochemical Effects of Methylenedioxymethamphetamine on Striatal
Monoaminergic Systems in the Rat Brain, Biochem. Pharmacol. 36 747-755
- This study compares the effects of MDMA and MDA on neurotransmitter release
in vitro and the (+) isomer is the more effective. The (+) isomer is also
the more effective in vivo.
- Schmidt, C.J., Vicki, L., Taylor, G.M. and Nieduzak, T.R. 5-HT-2 Antagonist
Stereoselectivly Prevents the Neurotoxicity of
3,4-Methylenedioxymethamphetamine by Blocking the Acute Stimulation of
Dopamine Synthesis: Reversal by L-DOPA. J. Pharm. Exptl. Therap. 256
- The effects of the optical isomers of a serotonin antagonist (one active,
the other inactive) on the interaction of MDMA with both the dopaminergic
and the serotoninergic systems of the male rat were studied. The protective
effects against forebrain serotonin deficit that was observed, was reversed
by the administration of L-DOPA.
- Schmidt, C.J., Wu, L. and Lovenberg, W. Methylenedioxymethamphetet-amine: A
Potentially Neurotoxic Amphetamine Analogue. Eur. J. Pharmacol. 124 175-178
- Acute administration of MDMA to rats provide selective and long lasting
serotonin and 5-HIAA depletion, similar to that produced by
p-chlorophenylalanine. There was an elevation of neostriatal dopamine as
well as it primary metabolite homovanillic acid. A typewritten draft of
this paper was presented to the DEA in conjunction with the legal hearings
held concerning the scheduling of MDMA.
- Seiden, L.S. Report of Preliminary Results on MDMA. Document entered into
evidence Re: MDMA Scheduling Docket No. 84-48, U.S. Department of Justice,
Drug Enforcement Administration, October 16, 1985.
- Rats were treated both acutely and chronically with MDMA, and the study of
the decrease of serotonin receptors and the interpretation of neurological
staining indicated a neurotoxicity similar to, but less dramatic than, that
seen with MDA.
- Slikker, Jr., W. and Gaylor, D.W. Biologically-Based Dose-Response Model
for Neurotoxicity Risk Assessment. Korean J. Toxicol. 6 205-213 (1990).
- A discussion of a model of risk assessment of neurotoxicity is presented,
illustrated by published experimental details from MDMA in experimental
- Slikker Jr., W., Ali, S.F., Scallet, A.C. and Frith, C.H.
Methylenedioxymethamphetamine (MDMA) Produces Long Lasting Alterations in
the Serotonergic System of Rat Brain. Soc. Neurosciences Abstrts. 12 101.7
- The chronic treatment of rats with MDMA (orally) produced decreased levels
of serotonin and 5-HIAA. At high dose levels there was a temporary decrease
in homovanillic acid (HVA) but no change in dopamine levels.
- Slikker Jr., W., Ali, S.F., Scallet, A.C., Firth, C.H., Newport, G.D. and
Bailey, J.R. Neurochemical and Neurohistological Alterations in the Rat and
Monkey Produced by Orally Administered Methylenedioxmethamphetamine (MDMA).
Toxicol Appl. Pharmacol. 94 448-457 (1988).
- A complete neurohistochemical study of chronically administered MDMA,
orally, to either rats of monkeys, showed extensive indications of
serotonin neuron involvement, but no changes in with either dopamine or its
- Slikker Jr., W., Holson, R.R., Ali, S.F., Kolta, M.G., Paule, M.G.,
Scallet, A.C., McMillan, D.E., Bailey, J.R., Hong, J.S. and Scalzo, F.M.
Behavioural and Neurochemical Effects of Orally Administered MDMA in the
Rodent and Nonhuman Primate. Neurotox. 10 529-542 (1989).
- MDMA was compared to p-chloroamphetamine (PCA) in rats following short-term
chronic oral administration. Observations were made on behavioural effects
and on neurochemical changes. Both compounds showed the "serotonin motor
syndrome" but these markers were not persistent, although the brain
serotonin level decreases were maintained with time. Similar decreases were
seen in monkeys, but there was no behavioural modification evident.
- Spanos, L.J. and Yamamoto, B.K. Methylenedioxymethamphetamine
(MDMA)-induced Efflux of Dopamine and Serotonin in Rat Nucleus Accumbens.
Soc. of Neurosciences Abstr. 12 p. 609 (#169.6) (1986).
- Following MDMA administration to rats, the efflux of dopamine was decreased
but then it quickly recovered. Serotonin depletion does not recover even
after 2 hours, thus MDMA may be neurotoxic.
- Steele, T.D., Brewster, W.K., Johnson, M.P., Nichols, D.E. and Yim, G.K.W.
Assessment of the Role of alpha-Methylepinine in the Neurotoxicity of MDMA.
Pharm. Biochem. Behav. 38 345-351 (1991).
- The catachol metabolite of MDMA, alpha-methylepinine, was evaluated as a
potential contributor to the neurotoxicity of MDMA. It was formed
metabolicially, and also assayed directly. No relationship to biogenic
amines was observed, and it appears not to be responsible for the observed
- Stone, D.M., Hanson, G.R. and Gibb, J.W. Does Dopamine Play a Role in the
Serotonergic "Neurotoxicity" Induced by 3,4-Methylenedioxymethamphetamine
(MDMA)? Soc. Neurosciences Abstrt. 12 169.4 (1986).
- The possibility that the negative serotonin effects of MDMA might be
mediated by dopamine was investigated. Studies involving dopamine synthesis
inhibitors and antagonists suggest less involvement of dopamine than is
seen with methamphetamine.
- Stone, D.M., Hanson, G.R. and Gibb, J.W. Differences in the Central
Serotonergic Effects of Methylenedioxymethamphetamine (MDMA) in Mice and
Rats. Neuropharm. 26 1657-1661 (1987).
- A number of studies as to the brain serotonin responses to MDMA (in rats)
suggest that the duration of exposure might be an important factor in the
estimation of toxic effects. Mice are shown to be less susceptible to MDMA,
neurotoxicologically, than rats.
- Stone, D.M., Merchant, K.M., Hanson, G.R. and Gibb, J.W. Immediate and Long
Term Effects of 3,4-Methylenedioxymethamphetamine on Serotonin Pathways in
Brain of Rat. Neuropharmacology 26 1677-1683 (1987).
- The time course for the decrease of markers of central serotonin function
in the rat is reported. Changes were observed at 15 minutes following a 10
mg/Kg s.c. injection, and much recovery was observed at the 2 week point.
Following multiple dose administration of MDMA, significant serotonin
changes were still evident after 110 days.
- Stone, D.M., Stahl, D.C., Hanson, G.R. and Gibb, J.W. The Effects of
3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-Methylenedioxyamphetamine
(MDA) on Monoaminergic Systems in the Rat Brain. Eur. J. Pharmacol. 128
- Single or multiple doses of either MDMA or MDA caused marked reduction in
both serotonin and 5-HIAA, as well as in the associated enzyme tryptophane
hydroxylase (TPH). Single injections elevated striatal dopamine
concentrations, although after repeated injections, these values became
normal. Striatal tyrosine hydroxylase (TH) was not changed.
- St. Omer, V.E.V., Ali, S.F., Holson, R.R., Duhart, H.M., Scalzo, F.M. and
Slikker, W. Behavioural and Neurochemical Effects of Prenatal
Methylenedioxymethamphetamine (MDMA) Exposure in Rats. Neurotox. Teratol.
13 13-20 (1991).
- Pregnant rats were treated repeatedly with MDMA. The progeny were
completely normal as to litter size, birth weight, physical appearance,
maturation parameters, and other measures of behaviour. No neurological
deficit could be observed, although the mother showed some decrease in
weight gain, and decreases in brain levels of serotonin at selected
- Takeda, H., Gazzara, R.A., Howard, S.G. and Cho, A.K. Effects of
Methylenedioxymethamphetamine (MDMA) on Dopamine (DA) and Serotonin (5-HT)
Efflux in the Rat Neostriatum. Fed. Proc. 45 1059 (#5266) April 13-18,
- Employing electrodes implanted in the neostriatum of anaesthetized rats,
the MDMA-induced efflux of dopamine and serotonin was measured. The
serotonin efflux was significantly increased by MDMA, and had returned to
normal by three hours. The dopamine efflux increased slightly, and then
dropped below normal. MDA decreased the dopamine efflux.
- Trulson, T.J. and Trulson, M.E. 3,4-Methylenedioxymethamphetamine (MDMA)
Suppresses Serotonergic Dorsal Raphe Neuronal Activity in Freely Moving
Cats and in Midbrain Slices in vitro. Soc. Neurosci. Abstr. Vol. 13, Part
3, p. 905 (1987) No. 251.7.
- A study of the decrease of brain serotonin levels in cats given 0.25-5.0
mg/Kg MDMA is reported. Pretreatment with p-chloroamphetamine greatly
attenuated the suppressant action of MDMA, and it is suggested that the
action of the two drugs is similar.
- Wagner, J. and Peroutka, S.J., Neurochemistry and Neurotoxicity of
Substituted Amphetamines, Neuropsychopharm. 3 219-220 (1990).
- MDMA was compared with Fenfluramine as a depletor of serotonergic nerve
terminals, as determined by the reduction of the density of paroxetine
binding sites in rat's brains. Single dosages of 30 mg/Kg and 10 mg/Kg were
required of the two drugs, respectively, to achieve significant changes.
- Whitaker-Azmitia, P.M. and Azmitia, E.C. A Tissue Culture Model of MDMA
Toxicity. The Clinical, Pharmacological and Neurotoxicological Effects of
the Drug MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka
- A procedure is described for studying MDMA toxicity employing tissue
cultures prepared from fetal rat brains. The similarities and the
differences observed between this technique and the more common in vivo
techniques, are discussed.
- Wilson, M.A., Ricaurte, G.A. and Molliver, M.E. The Psychotropic Drug
3,4-Methylenedioxymethamphetamine (MDMA) Destroys Serotonergic Axons in
Primate Forebrain: Regional and Laminar Differences in Vulnerability. Soc.
Neurosci. Abstr., Vol. 13, Part 3, No. 251.8 p. 905 (1987).
- The monkey shows a striking brain loss of serotonin terminals following
exposure to MDMA twice daily for 4 days at 5 mg/Kg. The distribution and
extent of this damage is reported.
- Wilson, M.A., Ricaurte, G.A. and Molliver, M.E. Distinct Morphologic
Classes of Serotoninergic Axons in Primates Exhibit Differential
Vulnerability to the Psychotropic Drug 3,4-Methylenedioxymethamphetamine.
Neuroscience 28 121 (1989).
- An exacting study is presented describing the morphological changes seen in
the serotoninergic axons in the monkey's brain following MDMA exposure.
- Woolverton, W.L., Virus, R.M., Kamien, J.B., Nencini, P., Johanson, C.E.,
Seiden, L.S. and Schuster, C.R. Behavioural and Neurotoxic Effects of MDMA
and MDA. Amer. Coll. Neuropsychopharm. Abstrts. p. 173 (1985).
- In behavioural studies in rats and monkeys trained to distinguish
amphetamine from saline, MDMA mimicked amphetamine. With chronic
administration, MDMA caused a degeneration of serotonin uptake sites, but
no change in affinity of the undamaged sites. These results were similar
to, but greater than, those seen with MDA.
- Yamamoto, B.K. and Spanos, L.J. The Acute Effects of
Methylenedioxymethamphetamine on Dopamine Release in the Awake-behaving
Rat. Eur. J. Pharmacol. 148 195-204 (1988).
- The effects of MDMA on the caudate and nucleus accumbens dopamine release
and metabolism were studied by in vivo voltammetry and HPLC with
electrochemical detection. There was a dose-dependent dopamine release
observed in both regions by both measures.
- Yeh, S.Y. Lack of Protective Effect of Chlorpromazine on
3,4-Methylenedioxymethamphetamine Induced Neurotoxicity on Brain Serotonin
Neurons in Rats. Res. Commun. Subst. Abuse 11 167-174 (1990).
- Studies involving the administration of MDMA with or without chlorpromazine
suggests have suggested that chlorpromazine does not protect MDMA-induced
depletion of serotonin in rats.
- Yeh, S.Y. and Hsu, F-L Neurotoxicity of Metabolites of MDA and MDMA
(Ecstasy) in the Rat. Soc. Neurosci. Abstr., Vol. 13, Part 3, p. 906 (1987)
- MDA, MDMA, and a number of potential metabolites (4-OH-3-OMe- amphetamine,
alpha-methyldopamine, alpha-methylnorepinephrine) were studied in the rat,
and the serotonin decreases measured. These metabolites have a lower
neurotoxicity than the parent compound.
- Zaczek, R., Culp, S. and De Souza, E.B. Intrasynaptosomal Sequestration of
[3H]Amphetamine and [3H]Methylenedioxyamphetamine: Characterization
Suggests the Presence of a Factor Responsible for Maintaining
Sequestration. J. Neurochem. 54 195-204 (1990).
- The incorporation of tritiated amphetamine, MDA and MDMA into rat brain
synaptosomes was studied. The observed dynamics is discussed in relationship
to the mechanism of action of amphetamine-induced monoamine release.
- Zaczek, R., Hurt, S., Culp, S. and DeSouza, E.B. Characterization of Brain
Interactions with Methylenedioxyamphetamine and
Methylenedioxymethamphetamine. NIDA Research Monograph Series #94 223-239
- Brain recognition sites have been described for labelled MDA and MDMA, and
similarities between these and the corresponding amphetamine sites are
- Zhao, Z., Castagnoli Jr., N, Ricaurte, G.A., Steele, T. and Martello, M.
Synthesis and Neurotoxicological Evaluation of Putative Metabolites of the
[(Methylenedioxy)methamphetamine]. Chem. Res. Toxicol. 5 89-94 (1992).
- A number of potential toxic metabolites of MDMA were synthesized and
assayed as neurotoxins. One of these, 2,4,5-trihydroxymethamphetamine, was
found to deplete both dopamine and serotonin.
[Section 5][Section 7]
E is for Ecstasy by Nicholas Saunders (firstname.lastname@example.org)
HTMLized by Lamont Granquist (email@example.com)