by Nicholas Saunders
[ Appendix 4 sec. 4 ] [ Index ] [ Appendix 4 sec 6 ]
Appendix 4: Bibliography Pharmacology
- Anderson III, G.M., Braun, G., Braun, U., Nichols, D.E. and Shulgin, A.T.
Absolute Configuration and Psychotomimetic Activity, NIDA Research
Monograph #22, pp 8-15 (1978).
- The "R" isomer of most chiral hallucinogenics is known to be the active
isomer. This generality includes LSD, DOB, DOM, DOET, and MDA. This
assignment has been demonstrated both in rabbit hyperthermia studies as
well as in clinical evaluations. With MDMA, however, this assignment is
reversed. In both rabbit and human studies, the more potent isomer of MDMA
is the "S" form, similar to that of amphetamine and methamphetamine. The
summed activity of the individual isomers did not satisfactorily reproduce
the activity of the racemic mixture. Also, the addition of an N-methyl to a
known hallucinogenic amphetamine routinely decreases the potency (as with
DOB, DOM, TMA and TMA-2). The exception again is with MDA, which produces
the equipotent MDMA. The relationship between the stimulants amphetamine
and methamphetamine is similar. The two drugs MDA and MDMA appear not to be
cross-tolerant in man. It is argued that the mechanisms of action of MDMA
must be different from that of MDA and related hallucinogenics.
- Beardsley, P.M., Balster, R.L. and Harris, L.S. Self-administration of
Methylenedioxymethamphetamine (MDMA) by Rhesus Monkeys. Drug and Alcohol
Dependence 18 149-157 (1986)
- In monkeys trained to self-administer cocaine intravenously MDMA was found,
in two out of four animals, to be an effective substitute.
- Beaton, J.M., Benington, F., Christian, S.T., Monti, J.A. and Morin, R.D.
Analgesic Effects of MDMA and Related Compounds. Pharmacologist 29 ABS 281
- Analgesia of several compounds (including MDMA and several close
homologues) was measured by the tail-flick response in mice. All produced
analgesia, with the (+) (S) MDMA being the most potent.
- Bilsky, E.J. and Reid, L.D. MDL-72222, A Serotonin 5-HT3 Receptor
Antagonist, Blocks MDMA's Ability to Establish a Conditioned Place
Preference. Pharm. Biochem. Behav. 39 509-512 (1991).
- MDMA has been shown to establish conditioned place-preference in rats. An
experimental 5-HT3 antagonist MDL-72222 blocked the effect, suggesting that
such antagonists might be of use in the evaluation the pharmacology of
- Bilsky, E.J., Hubbell, C.L., Delconte, J.D. and Reid, L.D. MDMA Produces a
Conditioned Place Preference and Elicits Ejaculation in Male Rats: A
Modulatory Role for the Endogenous Opioids. Pharm. Biochem. Behav. 40
- The ability of rats to establish a conditioned place-preference was
studied. This was blocked by the pre-administration of Naltrexone. This
drug interaction was studied as to ejaculatory behaviour, urination,
defecation and body weight change.
- Bilsky, E.J., Hui, Y., Hubbell, C.L. and Reid, L.D.
Methylenedioxymethamphet-amine's Capacity to Establish Place Preferences
and Modify Intake of an Alcohol Beverage. Pharmacol. Biochem. Behav. 37
- Employing behavioural studies with experimental rats, it was found that
MDMA led to a dose-dependent decrease of intake of sweetened ethanol.
Another study showed a positive, but not dose dependent, "conditioned
placement preference" test which, it is argued, provides further evidence
for the drug's abuse liability.
- Bird, M. and Kornetsky, C. Naloxone Antagonism of the Effects of MDMA
"Ecstasy" on Rewarding Brain Stimulation. The Pharmacologist 28 149 (1986).
- The lowering of the reward threshold (REBS, rewarding electrical brain
stimulation) by the s.c. administration of MDMA to rats (as determined by
implanted electrodes) was blocked by Naloxone. This suggests that MDMA
affects the same dopinergic and opioid substrates involved in cocaine and
- Braun, U., Shulgin, A.T. and Braun, G. Prufung auf zentral Aktivitat und
Analgesie von N-substituierten Analogen des Amphetamin-Derivates
3,4-Methylenedioxyphenylisopropylamin. Arzneim.-Forsch. 30 825-830 (1980).
- MDMA, and a large collection of N-substituted homologues, were assayed in
mice for both analgesic potency and enhancement of motor activity. MDMA
proved to be the most potent analgesic (compared with some 15 homologues)
but was not particularly effective as a motor stimulant. The structure and
pharmacological relationships to known analgesics are discussed.
- Brodkin, J., Malyala, A. and Nash, J.F. Effect of Acute Monamine Depletion
on 3,4-Methylenedioxymethamphetamine-Induced Neurotoxicity. Pharmacol.
Biochem. Behav. 45 647-53 (1993).
- The depletion of serotonin and dopamine induced by treatment of rats with
acute exposure to high levels of MDMA has been explored. Several
pharmacological probes have suggested that dopamine can play a major role
in the neurotoxic effects of MDMA.
- Callahan, P.M. and Appel, J.B. Differences in the Stimulus Properties of
3,4-Methylenedioxyamphetamine (MDA) and
N-Methyl-3,4-methylenedioxmethamphetamine (MDMA) in Animals Trained to
Discriminate Hallucinogens from Saline. Soc. Neurosci. Abstr.13, Part 3, p.
1720 (1987) No. 476.2.
- The stimulant properties of MDA and MDMA (including the optical isomers)
were studied in rats that were trained to discriminate mescaline or
(separately) LSD, from saline. "R"-MDA appears similar to both
hallucinogens, but the other isomers gave no clear-cut accord to the
literature reports of behavioural activity.
- Callahan, P.M. and Appel, J.B. Differences in the Stimulus Properties of
3,4-Methylenedioxyamphetamine and 3,4- Methylenedioxmethamphetamine in
Animals Trained to Discriminate Hallucinogens from Saline. J. Pharmacol.
Exptl. Therap. 246 866-870 (1988).
- In animals trained to discriminate LSD from saline, DOM, mescaline,
psilocybin and (+) MDA and both (+) and (-) MDMA, responses followed the
LSD cue. With animals trained to mescaline (vs. saline), both isomers of
both MDA and MDMA produced mescaline-like responses, as did DOM, LSD and
- Callaway, C.W., Wing, L.L. and Geyer, M.A. Serotonin Release Contributes to
the Locomotor Stimulant Effects of 3,4-Methylenedioxyamphetamine in Rats.
J. Pharm. Exptl. Therap. 254 456-464 (1990).
- The relative roles of dopamine and of serotonin have been evaluated,
employing the MDMA-induced locomotor hyperactivity in the rat. It has been
found that the observed activity calls upon mechanisms that depend upon the
release of central serotonin, as opposed to the mechanisms believed to
express amphetamine motor activity.
- Callaway, C.W. and Geyer, MA. Stimulant Effects of 3,
4-Methylenedioxymethamphetamine in the Nucleus Accumbens of Rat. Eur.
Journ. Pharm. 214 45-51 (1992)
- This study examined the behavioural effects in rats of intracerebral
administration of S-MDMA using an automated holeboard and open-field
apparatus. Administration of S-MDMA into the nucleus accumbens septi
produced locomotor hyperactivity.
- Callaway, C.W. and Geyer, M.A. Tolerance and Cross-Tolerance to the
Activating Effects of 3,4-Methylendioxymethamphetamine and a
5-Hydroxytryptamine1B Agonist. J. Pharmacol. Exptl. Therap. 263 318-326
- Two experiments were carried out. Changes in the response of rats to MDMA
were studied following chronic pretreatment with serotonin agonists
responsive to different receptor subtypes. And, following chronic
pretreatment with MDMA, changes in responses to these separate receptor
agonists were studied. There was an acute reciprocal cross-tolerance
observed between MDMA and RU-24969, a 5-HT1B receptor agonist, in producing
activating effects in the rat. This supports the hypothesis that the
release of endogenous serotonin increases locomotor activity by the
stimulation of 5-HT1b receptors.
- Cho, A.K., Hiramatsu, M., Kumagal, Y. and Patel, N. Pharmacokinetic
Approaches to the Study of Drug Action and Toxicity. NIDA Research
Monograph #136, pp 213-225 (1993). Ed. Linda Erinoff.
- Using rats as an experimental animal, the time courses of plasma MDMA and
metabolite MDA were reported following the administration of (separately)
(+) and (-) MDMA. The dideutero-analogue was used as an internal standard,
and the analysis was performed on the trifluoroacetamides by selected ion
monitoring. Microsomal metabolic pathways were also reported.
- Elayan, I., Gibb, J.W., Hanson, G.R., Foltz, R.L., Lim, H.K. and Johnson,
M. Long-term Alteration in the Central Monoaminergic Systems of the Rat by
2,4,5-Trihydroxyamphetamine but not by
2-Hydroxy-4,5-Methylenedioxyamphetamine. Eur. J. Pharmacol. 221 281-288
- The effects of the i.c.v. administration of three metabolites of MDMA were
studied in the rat. With 2,4,5-trihydroxyamphetamine there was a long-term
decline in tryptophane hydroxylase and tyrosine hydroxylase activity, as
well as a decrease in serotonin, dopamine and norepinephrin levels. This
suggests that this metabolite may contribute to the neurotoxic action of
MDMA on the serotonergic system.
- Crisp, T., Stafinsky, J.L., Boja, J.W. and Schechter, M.D. The
Antinociceptive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) in the
Rat. Pharmacol. Biochem. Behav. 34 497-501 (1989).
- MDMA was compared to morphine as an analgesic drug in the rat, in both the
tail-flick and the hot-plate tests. Both drugs were equipotent in the
latter tests, but only morphine was effective in the former test. The
effectiveness of MDMA was not attenuated by either the opiate antagonist
naltrexone nor the adrenoreceptor antagonist Phentolamine. However, the
serontin antagonist Methysergide did antagonise the MDMA effectiveness,
suggesting a serotonin involvement in this action.
- Davis, W.M. and Borne, R.F. Pharmacological Investigation of Compounds
Related to 3,4-Methylenedioxyamphetamine (MDA), Subs. Alc. Act/Mis. 5
- MDA and MDMA, as well as the homologous 3-aminobutanes HMDA and HMDMA, were
studied toxicologically in both isolated and aggregated mouse groups. Both
MDA and MDMA were of similar lethality in isolated animals (ca. 100 mg/Kg
i.p.) which was enhanced 3 or 4 fold by aggregation. The homologues HMDA
and HMDMA were approximately twice as toxic but showed no such enhancement.
The prelethal behaviour characteristics and the effects of potential
protective agents are described.
- Dimpfel, W., Spuler, M. and Nichols, D.E. Hallucinogenic and Stimulatory
Amphetamine Derivatives: Fingerprinting DOM, DOI, DOB, MDMA, and MBDB by
Spectral Analysis of Brain Field Potentials in the Freely Moving Rat
(Tele-Stereo-EEG). Psychopharmacology 98 297-303 (1989).
- Recording from several areas of the brain of freely moving rats were made
following the administration of several hallucinogens and other
structurally related entactogens and stimulants. The recorded results show
clear regional specificity of the various classes of drugs, and suggest
that serotonin receptors in the striatum might be involved with
- Dragunow, M., Logan, B. and Laverty, R. 3,4-Methylenedioxymeth-amphetamine
Induces Fos-like Proteins in Rat Basic Ganglia: Reversal with MK-801. Eur.
J. Pharmacol. 206 205 (1991).
- Administration of MDMA to rats leads to an accumulation of Fos proteins and
Fos-related antigens. The NMDA antagonist MK-801 inhibited this induction,
but Fluoxetine had no effect.
- Evans, S.M. and Johanson, C.E. Discriminative Stimulus Properties of
(+/-)-Methylenedioxyamphetamine in Pigeons. Drug and Alcohol Dependence 18
- Pigeons were trained to discriminate (+) amphetamine from saline. Both MDA
and MDMA substituted for amphetamine, and both were less potent.
- Farfel, G.M., Vosmer, G.L. and Seiden, L.S. The N-Methyl-D-Aspartate
Antagonist MK-801 Protects Against Serotonin Depletions Induced by
Methamphetamine, 3,4-Methylenedioxymethamphetamine and p-Chloramphetamine.
Brain Res. 595 121-127 (1992).
- The NMDA receptor antagonist MK-801 attenuates the decrease in serotonin
concentration brought about by MDMA and two other amphetamine derivatives,
in rats. Changes in the serotonin metabolite 5-hydroxyindoleacetic acid
concentrations were similar to the serotonin in changes observed.
- Fellows, E.J. and Bernheim, F. The Effect of a Number of Aralkylamines on
the Oxidation of Tyramine by Amine Oxidase. J. Pharm. Exptl. Therap. 100
- There were animal behavioural studies made on the chain homologue of MDMA,
vis., 1-(3,4-methylenedioxyphenyl)-3-methylaminobutane. This is the amine
that would result from the use of the "wrong" piperonylacetone in illicit
synthesis. In the dose range 10-25 mg/Kg, toxic effects such as tremors and
convulsions were seen.
- Finnegan, K.T., Calder, L., Clikeman, J., Wei, S. and Karler, R. Effects
of L-type Calcium Channel Antagonists on the Serotonin-depleting Actions of
MDMA in Rats. Brain Res. 603 134-138 (1993).
- Of several calcium channel blockers effective at increasing the convulsion
threshold induced by NMDA, only flunarizine blocked the long-term serotonin
depleting effects of MDMA. It is suggested that calcium channels are not
involved in the neurotoxicity of MDMA.
- Gazzara, R.A., Takeda, H., Cho, A.K. and Howard, S.G. Inhibition of
Dopamine Release by Methylenedioxymethamphetamine is Mediated by Serotonin,
Eur. J. Pharmacol. 168 209-217 (1989).
- The administration of MDMA to rats produces a long-lasting decrease in
extracellular dopamine in brain tissues. To determine if the known
increased release of serotonin might be the cause of this, experimental
animals were pretreated with PCA which effectively decreased the serotonin
content and inhibited the dopamine decrease following MDMA treatment. The
serotonin release by MDMA is argued as possibly being a mediating factor in
the observed dopamine release.
- Gibb, J.W., Johnson, M., Stone, D.M. and Hanson, G.R. Mechanisms Mediating
Biogenic Amine Deficits Induced by Amphetamine and its Congeners. NIDA
Research Monograph #136 226-241 (1993).
- A large number of amphetamine-like derivatives, including MDMA, have been
compared for their capacity for causing neurochemical deficits, in both the
serotonin and the dopamine systems. Neurotoxicity is inferred in most
cases as there is a long-term persistence of change.
- Glennon, R.A. and Misenheimer, B.R. Stimulus Effects of
N-Monoethyl-1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDE) and
N-Hydroxy-1-(3,4-Methylenedioxyphenyl)-2-aminopropane (N-OH MDA) in Rats
Trained to Discriminate MDMA from Saline. Pharmacol. Biochem. Behav. 33
- Both MDE and MDOH generalized to MDMA in rats trained to discriminate MDMA
from saline. Amphetamine was less effective. Since MDMA substitutes for
amphetamine, whereas neither MDE nor MDOH do so, these latter drugs appear
to have less of an amphetamine-like component than MDMA.
- Glennon, R.A. and Young, R. Further Investigation of the Discriminative
Stimulus Properties of MDA. Pharmacol. Biochem. and Behaviour 20, 501-505
- In rats trained to distinguish between racemic MDA (and separately,
"S"-amphetamine) and saline, MDMA (as well as either optical isomer of MDA)
was found to generalize to MDA. Similarly, with rats trained to distinguish
between dextro-amphetamine and saline, MDMA and "S"-MDA (but not "R"-MDA or
"S"-DOM) produced generalization responses.
- Glennon, R.A., Little, P.J., Rosecrans, J.A. and Yousif, M. The Effects of
MDMA ("Ecstasy") and its Optical Isomers on Schedule-Controlled Responding
in Mice. Pharmacol. Biochem. Behav. 26 425-426 (1987).
- The effectiveness of several analogs of MDMA were evaluated in mice trained
in a reinforcement procedure. Both (+) and racemic MDMA were 4x the potency
of the levo-isomer; all were less potent than amphetamine.
- Glennon, R.A., Young, R., Rosecrans, J.A. and Anderson, G.M. Discriminative
Stimulus Properties of MDA Analogs. Biol. Psychiat. 17 807-814 (1982).
- In rats trained to distinguish between the psychotomimetic DOM and saline,
several compounds were found to generalize to DOM (including racemic MDA,
its "R" isomer, and MMDA-2) Others did not generalize to DOM (including
MDMA, the "S" isomer of MDA, and homopiperylamine). These results are
consistent with the qualitative differences reported in man.
- Glennon, R.A., Yousif, M. and Patrick, G. Stimulus Properties of
1-(3,4-Methylenedioxy)-2-Aminopropane (MDA) analogs. Pharmacol. Biochem.
Behav. 29 443-449 (1988).
- Rats were trained to discriminate between saline and DOM or d-amphetamine.
They were challenged with "R" and "S" MDMA, with racemic, "R" and "S" MDE,
and with racemic MDOH (N-OH-MDA). The amphetamine-trained animals
generalized to "S" MDMA, but to neither "R" MDMA, any of the MDE isomers,
MDOH, nor to homopiperonylamine. N-substituted amphetamine derivatives
(N-ethyl and N-hydroxy) also gave the amphetamine response, but none of
these compounds generalized to DOM. This study supports the suggestion that
MDMA represents a class of compounds apart from the stimulant or the
- Glennon, R.A. MDMA-Like Stimulus Effects of Alpha-Ethyltryptamine and the
Alpha-Ethyl Homolog of DOM. Pharmacol. Biochem. Behav. 46 459-462 (1993).
- The alpha-ethyl homologues of alpha-methyltryptamine and of DOM are a-ET
and Dimoxamine. Whereas rats trained to discriminate MDMA from saline
failed to generalize to DOM or alpha-methyltryptamine, they did to both of
- Glennon, R.A. and Higgs, R. Investigation of MDMA-Related Agents in Rats
Trained to Discriminate MDMA from Saline. Pharm. Biochem. and Behav. 43
- A number of MDMA metabolites and related compounds were compared to MDMA in
discrimination studies in the rat. Several gave MDMA-appropriate
responses, but only 4-methoxymethamphetamine showed stimulus
generalization. The intact methylenedioxy ring appears unneccessary for
- Glennon, R.A., Higgs, R., Young, R. and Issa, H. Further Studies on
N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane as a Discriminative
Stimulus: Antagonism by 5-Hydroxytryptamine3 Antagonists. Pharmacol.
Biochem. Behavior 43 1099-106 (1992).
- Rats were trained to discriminate MDMA from saline, and this response was
evaluated with the study of antagonists of 5-HT1A (NAN-190), 5-HT2
(pirenperone), 5-HT3 (zacopride) and dopamine receptors (haloperidol). The
results can give rise to several mechanistic interpretations, but it is
concluded that MDMA produces it's stimulus effects via a complex mechanism
involving both dopaminergic and serotonergic components.
- Gold, L.H. and Koob, G.F. Methysegide Potentialtes the Hyperactivity
Produced by MDMA in Rats. Pharmacol. Biochem. Behav. 29 645-648 (1988).
- The hyperactivity that results from MDMA administration is significantly
increased by methysergide. This latter drug was itself without effect, nor
did it potentiate the hyperactivity induced by amphetamine administration.
- Gold, L.H. and Koob, G.F. MDMA Produces Stimulant-like Conditioned
Locomotor Activity, Psychopharmacology 99 352-356 (1989).
- The administration of MDMA to rats concurrently with exposure to specific
sensory clues (odours) produced a conditioned activity response to the
clues alone. In this property, MDMA resembles other psychostimulants such
as amphetamine and cocaine.
- Gold, L.H., Geyer, M.A. and Koob, G.F. Psychostimulant Properties of MDMA.
NIDA Monograph #95. Problems of Drug Dependence 345-346 (1989).
- The pharmacological stimulant properties of MDMA are compared with those of
amphetamine. But, as there are some hallucinogenic activity apparent as
well, the overall action may be considered as unique mixture of these two
- Gold, L.H., Geyer, M.A. and Koob, G.F. Neurochemical Mechanisms Involved in
Behavioural Effects of Amphetamines and Related Designer Drugs. NIDA
Monograph #94. Pharmacology and Toxicology of Amphetamines and Related
Designer Drugs, 101-126 (1989).
- The dopaminergic aspects of the stimulatory action of MDMA, MDE and
amphetamine in rats is discussed. This motor action has been evaluated in
conjunction with several areas of brain neuroactivation.
- 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
- The stimulant action produced by MDMA in rats was studied with and without
the brain lesions produced by 6-hydroxydopamine. The attenuation of
responses was similar to that seen with amphetamine suggests that some
involvement of presynaptic release of dopamine may be involved in its
- Gordon, C.J., Watkinson, W.P., O'Callaghan, J.P. and Miller, B.D. Effects
of 3,4-Methylenedioxymethamphetamine on Autonomic Thermoregulatory
Responses of the Rat. Pharm. Biochem. Behav. 38 339-344 (1991).
- The acute s.c. administration of 30 mg/Kg MDMA to rats led to a increase in
body temperature. It is concluded that MDMA stimulates the serotonin
pathways that control the metabolic rate and this, accompanied by
peripheral vasostriction, lead to the observed hyperthermia.
- Gough, B., Ali, S.F., Slikker, W. and Holson, R.R. Acute Effects of
3,4-Methylenedioxymethamphetamine (MDMA) on Monoamines in Rat Caudate.
Pharmacol. Biochem. Behav. 39 619-623 (1991).
- A number of neurotransmitter metabolites were assayed in the rat, following
the i.p. injection of MDMA. It was concluded that MDMA affects both the
dopaminergic as well as the serotoninergic systems.
- Griffiths, R.R., Lamb, R. and Brady, J.V. A Preliminary Report on the
Reinforcing Effects of Racemic 3,4-Methylenedioxymethamphetamine in the
Baboon. Document entered into evidence Re: MDMA Scheduling Docket No.
84-48, U.S. Department of Justice, Drug Enforcement Administration, October
- In three baboons trained to respond to cocaine, MDMA maintained
self-administration at a somewhat lower level than cocaine, d-amphetamine,
and phencyclidine. There was the evocation of distinct behavioural signals,
which suggested that MDMA had a high abuse potential.
- Harris, L.S. Preliminary Report on the Dependence Liability and Abuse
Potential of Methylenedioxymethamphetamine (MDMA). Document entered into
evidence Re: MDMA Scheduling Docket No. 84- 48, U.S. Department of Justice,
Drug Enforcement Administration, October 16, 1985.
- MDMA and amphetamine were compared as to locomotor activity in mice, and in
reinforcing activity in monkeys as compared to cocaine. MDMA showed a
fraction (20-25%) of the stimulant activity of amphetamine, and was
substituted for cocaine in some of the test monkeys.
- Hashimoto, K. Effects of Benzylpiperazine Derivatives on the Acute Effects
of 3,4-Methylenedioxymethamphetamine in Rat Brain. Neurosci. Let. 152
- The reduction of serotonin in rat brain following exposure to MDMA was
significantly attenuated with the co-administration of weak inhibitors
(several benzylpiperazines) of serotonin uptake into synaptosomes. The
co-administration of the more potent inhibitors (desipramine, imipramine)
did not attenuate this MDMA-induced reduction of serotonin, suggesting that
the effects of the piperazines may employ a different neurological pathway.
- Hashimoto, K., Maeda, H., Hirai, K. and Goromaru, T. Drug Effects on
Distribution of [3H]3,4-Methylenedioxymethamphetamine in Mice. Eur. J.
Pharmacol. - Environm. Tox. Pharmacol. Section 228 247-256 (1993).
- The effectiveness of a number of drugs and other compounds carrying the
methylenedioxyphenyl group on the distribution of radioactive MDMA in the
mouse brain was determined. It is suggested that there may exist a
specific mechanism for this group which rapidly alters the disposition and
metabolism of MDMA.
- Hegadoren, K.M., Baker, G.B. and Coutts, R.T. The Simultaneous Separation
and Quantitation of the Enantiomers of MDMA and MDA using Gas
Chromatography with Nitrogen-Phbosphorus Detection. Res. Commun. Subs.
Abuse 14 67-80 (1993).
- Following the administration of racemic MDMA to the rat, the levels of both
MDMA and its demethylated metabolite MDA were determined in areas of the
brain. Assays were made at 1,2,4 and 8 hrs., and with a chiral derivative
system that allowed the determination of the amounts of the optical isomers
resulting from selective chiral metabolism. For unmetabolized MDMA, the
concentrations of the (-) isomer were greater than for the (+) isomer. The
reverse was true for the demethylated metabolite MDA which, although
present at much lower levels, was largely the (+) isomer in all regions
- Hiramatsu, M., Nabeshima, T., Kameyama, T., Maeda, Y. and Cho, A.K. The
Effect of Optical Isomers of 3,4-Methylenedioxymethamphetamine (MDMA) on
Stereotyped Behaviour in Rats. Pharmacol. Biochem. Behaviour 33 343-347
- The optical isomers of MDMA were compared as to their potencies in inducing
stereotyped behaviour in rats. The "S", or (+) isomer was the more potent,
which was consistent with this isomer's increased effectiveness in the
release of neurotransmitters.
- Hubner, C.B., Bird, M., Rassnick, S. and Lornetsky, C. The Threshold
Lowering Effects of MDMA (Ecstasy) on Brain-stimulating Reward.
Psychopharmacology 95 49-51 (1988).
MDMA produced a dose-related lowering of the reward threshold, as
- determined in rats with electrodes stereotaxically implanted in the medial
forebrain bundle-lateral hypothalamic area. This procedure has been used as
an animal model for drug-induced euphoria.
- Huang, X. and Nichols, D. 5-HT2 Receptor-Mediated Potentiation of Dopamine
Synthesis and Central Serotonergic Deficits. Eur. J. Pharm. 238 291-296
- Employing receptor agonists, releasing agents and enzyme inhibitors in
rats, the hypothesis was tested that serotonin modulates the MDMA-induced
increase in dopamine synthesis. The results indicate that the induced
increases depend on both serotonin receptor stimulation and on dopamine
- Jensen, K.F., Olin, J., Haykal-Coates, N., O'Callaghan, J., Miller, D.B.
and de Olmos, J.S. Mapping Toxicant-Induced Nervous System Damage With
Cupric Silver Stain: A Quantitative Analysis of Neural Degeneration
Induced by 3,4-Methylenedioxymethamphetamine. NIDA Research Monograph #136
- An argument is made for the quantitative potential that could be realized
from the cupric silver staining of degenerating neurons. This technique
was applied to rats that had been treated with MDMA and a dose-response
curve of neural degeneration was obtained.
- Johnson, M., Bush, L.G., Gibb, J.W. and Hanson, G.R. Blockade of the
3,4-Methylenedioxymethamphetamine-induced Changes in Neurotensin and
Dynorphin A Systems. Eur. J. Pharmacol. 193 367-370 (1991).
- The increase in immunoreactivity in the neurotensin and dynorphin systems
following a single s.c. injection of MDMA in the rat has suggested that both
the dopaminergic and glutamatergic systems are involved.
- Johnson, M.P., Frescas, S.P., Oberlender, R. and Nichols, D.E. Synthesis
and Pharmacological Examination of
5-Methoxy-6-methyl-2-aminoindane: Similarities to
3,4-Methylenedioxymeth-amphetamine (MDMA). J. Med. Chem. 34 1662-1668
- The two title compounds have been viewed as analogues of DOM (missing a
methoxyl group) or of alpha,4-dimethyltyramine (with O-methylation) and
have been synthesized. Both compounds appear to be pharmacologically
similar to MDMA, but are lacking any indications of neurotoxicity.
- Johnson, M., Bush, L.G., Midgley, L., Gibb, J.W. and Hanson, G.R. MK-801
Blocks the Changes in Neurotensin Concentrations Induced by
Methamphetamine, 3,4-Methylenedioxymethamphetamine, Cocaine, and GBR 12909.
Ann. N.Y. Acad. Sci. 668 350-352 (1992).
- A study of the neurotensin-like immunoreactivity in the rat has been shown
to increase following the administration of several compounds, including
MDMA. This can be blocked by the administration of a dopamine D1 receptor
antagonist (SCH 23390).
- Kamien, J.B., Johanson, C.E., Schuster, C.R. and Woolverton, W.L. The
Effects of (+/-)-Methylenedioxymethamphetamine in Monkeys Trained to
Discriminate (+)-Amphetamine from Saline. Drug and Alcohol Dependence 18
- In monkeys trained to discriminate between amphetamine and saline, MDMA
substituted for amphetamine suggesting that there was an amphetamine-like
component to its action. This similarity suggested a dependence potential.
- Kasuya, Y. Chemicopharmacological Studies on Antispasmodic Action. XII.
Structure-Activity Relationship on Aralkylamines. Chem. Pharm. Bull. 6
- In vitro studies on mouse intestinal segments were carried out for the
chain homologue of MDMA, vis.,
1-(3,4-methylenedioxyphenyl)-3-methylaminobutane. This is the amine that
would result from the use of the "wrong" piperonylacetone in illicit
synthesis. The compound shows weak atropine action.
- Kehne, J.H., McCloskey, T.C., Taylor, V.L., Black, C.K., Fadayel, G.M. and
Schmidt, C.J. Effects of the Serotonin Releasers
3,4-Methylenedioxymethamphetamine (MDMA), 4-Chloroamphetamine (PCA) and
Fenfluramine on Acoustic and Tactile Startle Reflexes in Rats. J. Pharm.
Exptl. Therap. 260 78-89 (1992).
- The three amphetamine derivatives, MDMA, PCA and Fenfluramine share a
common neurochemical action, of releasing central cerotonin, but the
behavioural effects they evoke are dissimilar. Use of serotonin blockers
was made to study the pharmacology of these compounds.
- Krebs, K.M. and Geyer, M.A. Behavioral Characterization of
Alpha-Ethyltryptamine, a Tryptamine Derivative with MDMA-like Properties in
Rats. Psychopharmacology 113 284-287 (1993).
- There have been a number of anecdotal comparisons between MDMA and
alpha-ethyl tryptamine (AET). These have supported the scheduling of the
latter compound in the United States. In rat studies, AET appears to
produce an MDMA-like profile of behavioral changes apparently related to
- Kulmala, H.K., Boja, J.W. and Schechter, M.D. Behavioural Suppression
Following 3,4-Methylenedioxymethamphetamine. Life Sciences 41 1425-1429
- Rotation in rats was employed as an assay of the central dopaminergic
activity of MDMA. At low doses it acts similarly to amphetamine, but at
higher doses it appears to stimulate the dopamine receptor directly.
- Lamb, R.J. and Griffiths, R.R. Self-injection of
dl-3,4-Methylenedioxymethamphetamine in the Baboon. Psychopharmacolgy 91
- In monkeys conditioned to the self-administration of cocaine, MDMA produced
a similar but less potent response. A decrease in food intake was also
- LeSage, M., Clark, R. and Poling, A. MDMA and Memory: The Acute and
Chronic Effects of MDMA in Pigeons Performing under a
Delayed-matching-to-sample Procedure. Psychopharmacol. 110 327-332 (1993).
- The behavior-disruptive effectiveness of MDMA in the conditioned behavior
of pigeons was found to be dose-dependent. Tolerance to the drug was
observed, but there did not appear to be any long-lasting behavioral
- Li, A., Marek, G., Vosmer, G. and Seiden, L. MDMA-induced Serotonin
Depletion Potentiates the Psychomotor Stimulant Effects of MDMA on Rats
Performing on the Differential-Reinforcement-of-Low-Rate (DRL) Schedule.
Society of Neurosciences Abstracts 12 169.7 (1986).
- This is a study of Serotonin depletion and motor response. The long term
depletion following both acute and chronic administration of MDMA to rats,
increased activity and decreased serotonin suggests some inhibitory action
of this neurotransmitter.
- Li, A.A., Marek, G.J., Vosmer, G. and Seiden, L.S. Long-Term Central 5-HT
Depletions Resulting from Repeated Administration of MDMA Enhances the
Effects of Single Administration of MDMA on Schedule-Controlled Behaviour
of Rats Pharmacol. Biochem. Behaviour 33 641-648 (1989).
- Experimental rats showed an increased response in schedule-controlled
behaviour studies to the effect of a single dose of MDMA if this dose was
preceded by a regimen of chronic exposure to MDMA. This sensitisation was
typical of amphetamine and other stimulants.
- Matthews, R.T., Champney, T.H. and Frye, G.D. Effects of
(+/-)-Methylenedioxymethamphetamine (MDMA) on Brain Dopaminergic Activity
in Rats. Pharmacol. Biochem. Behav. 33 741-747 (1989).
- High levels of MDMA in rats increased locomotor activity, and decreased
brain dopamine turnover rate as determined by dihydroxyphenylacertic acid
levels. There were some similarities to amphetamine exposure in the effects
seen on dopamine neurons.
- Mansbach, R.S., Braff, D.L. and Geyer, M.A. Prepulse Inhibition of the
Acoustic Startle Response is Disrupted by
N-Ethyl-3,4-methylenedioxyam-phetamine (MDEA) in the Rat. Eur. J.
Pharmacol. 167 49-55 (1989).
- Both the optical isomers and the racemate of MDE, as well as racemic MDMA,
were studied as to their effectiveness as prepulse inhibitors of the
acoustic startle response, a measure of sensitivity to psychoactive drugs.
The (+) isomer of MDE, and the racemate, and (less so) racemic MDMA were
effective inhibitors, suggesting a psychostimulant component in their
- McKenna, D.J., Guan, X.-M. and Shulgin, A.T. 3,4-Methylenedioxyamphetamine
(MDA) Analogues Exhibit Differential Effects on Synaptosomeal Release of
3H-Dopamine and 3H-5-Hydroxytryptamine. Pharm. Biochem. Behav. 38 505-512
- The in vitro effectiveness of a number of MDA analogues on the release of
serotonin and dopamine from synaptosomes was determined.
- Nash, J. F. Ketanserin Pretreatment Attenuates MDMA-induced Dopamine
Release in the Striatum as Measured by in vivo Microdialysis. Life Sciences
47 2401-2408 (1990).
- The systemic administration of MDMA to freely moving rats produces a
dose-dependent extracellular concentration of dopamine in the striatum. The
effects of administering the serotonin antagonist, Ketanserin, are
- Nash, J.F. and Brodkin, J. Microdialysis Studies on
3,4-Methylenedioxymethamphetamine-induced Dopamine Release: Effect of
Dopamine Uptake Inhibitors. J. Pharm. Exptl. Therap. 259 820-825 (1991)
- The effects of both dopamine and serotonin uptake inhibitors on the MDMA
induced increase in dopamine efflux were studied by microdialysis
techniques. The dopaminergic effects are believed to be independent of
those resulting from serotonin release.
- Nash, J.F. and Nichols, D.E. Microdialysis Studies on
3,4-Methylenedioxyamphetamine and Structurally Related Analogues. Europ. J.
Pharmacol. 200 53-58 (1991).
- MDA and three analogues (MDMA, MDE and MBDB) were studied in the
free-moving rat by microdialysis. The effects on dopamine were observed,
and they did not correlate well with serotonin. Structural relationships
- Nash Jr., J.F., Meltzer, H.Y. and Gulesky, G.A. Elevation of Serum
Prolactin and Corticosterone Concentrations in the Rat after the
Administration of 3,4-Methylenedioxymethamphetamine. J. Pharmacol. Exptl.
Therap. 245 873-879 (1988).
- The effects of acute i.p. administrations of MDMA were seen as an elevation
of prolactin and corticosterone in rats. The effects of the serotonin
uptake inhibitor Fluoxetine and of p-chlorophenylalanine on MDMA-induced
neuroendocrine responses are similar to those induced by
- Nencini, P., Woolverton, W.L. and Seidin, L.S. Enhancement of
Morphine-induced Analgesia after Repeated Injections of
Methylenedioxymethamphetamine. Brain Research 457 136-142 (1988).
- Chronic administration of MDMA to rats led to an enhancement of the
analgesic effects of morphine administration. The changes in the serotonin
and 5-hydroxytryptamine levels were confirmed.
- Nichols, D.E., Hoffman, A.J., Oberlender, R.A., Jacob III, P. and Shulgin,
A.T. Derivatives of 1-(1,3-Benzodioxol-5-yl-2-butanamine: Representatives
of a Novel Therapeutic Class. J. Med. Chem. 29 2009-2015 (1986).
- Animal discrimination studies (LSD versus saline) of the alpha-ethyl
homologues of MDA and MDMA were performed. No generalization occurred with
the N-methyl analogs of either group (MDMA and MBDB), and the latter
compound was also found to be psychoactive but not hallucinogenic in man.
It was found to be less euphoric than MDMA, but with the same sense of
empathy and compassion. The term "entactogen" is proposed for the class of
drugs represented by MDMA and MBDB.
- Oberlender, R. and Nichols, D.E. Drug Discrimination Studies with MDMA and
Amphetamine. Psychopharmacology 95 71-76 (1988).
- Rats were trained to discriminate saline from either racemic MDMA or
dextroamphetamine. The MDMA cue generalized to MDA and to all isomers of
MDMA and MBDB, but not to LSD or DOM. The dextroamphetamine cue generalized
to methamphetamine, but to none of the forms of either MDMA or MBDB. The
"S" isomers of both MDMA and MBDB were the more potent.
- Oberlender, R. and Nichols, D.E.
(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a Discriminative Stimulus in Studies of
3,4-methylenedioxymethamphetamine-Like Behavioural Activity. J. Pharm.
Exptl. Therap. Vol. 255 pp.1098-1106 (1990).
- A number of compounds (including the racemate and the optical isomers of
MBDB) were studied in rats trained to discriminate between (+)-MBDB and
saline. There was generalization to both MDMA and MDA, but not to DOM, LSD
or mescaline, nor for either amphetamine or methamphetamine. Several
aminoindanes were also assayed.
- Park, W.K. and Azmitia, E.C. 5-HT, MDMA (Ecstasy), and Nimodipine Effects
on 45Ca-Uptake into Rat Brain Synaptosomes. Ann. N.Y. Acad. Sci. 635
- The uptake of calcium ion into the rat brain, both basal and K+ stimulated,
was increased by exposure to MDMA, a potent neuropathological drug of
abuse. Interestingly, this same increase was seen with both serotonin and
- Paulus, M.P. and Geyer, M.A. The Effects of MDMA and Other
Methylenedioxy-substituted Phenylalkylamines on the Structure of Rat
Locomotor Activity. Neuropsychopharm. 7 15-31 (1992).
- The effects of acute s.c. injections of MDA, racemic, S(+) and R(-) MDMA,
racemic MBDB, racemic MDEA, DOI, and methamphetamine were studied in the
rat. Indirect 5-HT1 effects appear to contribute substantially to the
differential changes in the amount and structure of motor behaviour induced
by the phenylalkylamines. This conclusion may provide an encouraging
rationale to develop postsynaptically effective "entactogens", a potential
new drug category as adjunctive psychotherapeutics.
- Paulus, M.P., Geyer, M.A., Gold, L.H. and Mandell, A.J. Application of
Entropy Measurements Derived from the Ergodic Theory of Dynamical Systems
to Rat Locomotor Behaviour. Proc. Natl. Acad. 87 723-727 (1990).
- The observed activity of rats treated with MDMA followed paths with a
different geometric distribution, than control animals treated with
- Rezvani, A.H., Garges, P.L., Miller, D.B. and Gordon, C.J. Attenuation of
Alcohol Consumption by MDMA (Ecstasy) in Two Strains of Alcohol-preferring
Rats. Pharm. Biochem. Behav. 43 103-110 (1992)
- The hypothesis that serotonin is involved in alcoholism has led to the
design and carrying out of an experiment evaluating the action of MDMA,
acutely and chronically, on the behaviour of alcohol-preferring rats. It
was found to have an inhibitory action on alcohol preference, perhaps by
the enhancement of serotonergic and/or dopaminergic systems in the CNS.
- Rosecrans, J.A. and Glennon, R.A. The Effect of MDA and MDMA ("Ecstasy")
Isomers in Combination with Pirenpirone on Operant Responding in Mice.
Pharmacol. Biochem. Behav. 28 39-42 (1987). See also: Soc. Neurosci. Abstr.
13, Part 3, p. 905 (1987) No. 251.10.
- The disruptive effects of the optical isomers of MDA and MDMA were studied
for mice trained in a reinforcement schedule, both with and without
pretreatment with Pirenpirone, a serotonin antagonist. Of the four isomers
evaluated, only "R"-MDA behaviour responses were attenuated by Pirenpirone.
- Scallet, A.C., Lipe, G.W., Ali, S.F., Holson, R.R., Frith, C.H. and Slikker
Jr., W. Neuropathological Evaluation by Combined Immunohistochemistry and
Degeneration-Specific Methods: Application to
Methylenedioxymethamphetamine. Neurotoxicol. 9 529-539 (1988).
- The combination of neurohistological and neurochemical evaluations suggests
that the changes in serotonin levels following MDMA exposure in the rat is
due to neural degeneration followed by axon loss, rather than a decrease in
- Scanzello, C.R., Hatzidimitriou, G., Martello, A.L., Katz, J.L. and
Ricaurte, G.A. Serotonergic Recovery after
(+/-)3,4-(Methylenedioxy)methamphetamine Injury: Observations in Rats. J.
Parmacol. Exptl. Therap. 264 1484-1491 (1993).
- In rats, as opposed to monkeys, the damage that is done by exposure to MDMA
appears to be reversable. This study explored the permanence of this
recovery, and in some cases it appears to be sustained for at least a year.
Some rats, however, appeared not to show this recovery.
- Schmidt, C.J., Sullivan, C.K. and Fadayel, G.M. Blockade of Striatal
5-Hydroxytryptamine(2) Receptors Reduces the Increase in Extracellular
Concentrations of Dopamine Produced by the Amphetamine Analogue
3,4-Methylenedioxymethamphetamine. J. Neurochem. 62 1382-89 (1994).
- MDMA stimulates the synthesis and release of dopamine, and serotonin
receptor antagonists interfere with this action. Studies have been made to
determine which receptors are responsible.
- Schechter, M.D. Discriminative Profile of MDMA. Pharmacol. Biochem. Behav.
24 1533-1537 (1986)
- Rats trained to discriminate several psychoactive drugs (against saline)
were challenged with MDMA. The findings show that MDMA may act both as a
dopamine and a serotonin agonist. This property is related to its abuse
- Schechter, M.D. MDMA as a Discriminative Stimulus: Isomeric Comparisons.
Pharmacol. Biochem. Behav. 27 41-44 (1987).
- Studies with rats trained to discriminate racemic MDMA from saline, showed
generalization with both optical isomers of MDMA, with the "S" isomer being
more potent. The chronological observations paralleled the reported human
- Schechter, M.D. Advantages and Disadvantages of a Rapid Method to Train
Drug Discrimination. Pharmacol. Biochem. Behav. 31 239-242 (1988).
- A exploration of training regimens was made for accelerating the
development of discrimination protocols, using MDMA as a trial drug. The
various findings are discussed.
- Schechter, M.D. Effect of MDMA Neurotoxicity Upon Its Conditioned Place
Preference and Discrimination. Pharmacol. Biochem. Behav. 38 539-544
- Two behaviour patterns, conditioned place preference and discrimination,
were used as measures of the neurotoxicity induced by MDMA in rats.
Dose-dependent changes were observed. The possible involvement of both
serotonin and dopamine neurons is discussed.
- Schlemmer Jr., R.F., Montell, S.E. and Davis, J.M. Fed. Proc. 45 1059 (1986).
- The behavioural effects of MDMA have been studied in a primate colony,
following multiple acute exposures. There was a decrease in activity,
grooming, and food-searching, and an increase in staring. There was a
disruption of social behaviour, that differed from the effects of other
- Schmidt, C.J. and Taylor, V.L. Reversal of the Acute Effect of
3,4-Methylenedioxymethamphetamine by 5-HT Uptake Inhibitors. Europ. J.
Pharmacol. 181 133-136 (1990).
- Re-uptake inhibitors of serotonin were administered at intervals following
the administration of MDMA to rats. The inactivation of tryptophan
hydroxylase activity that follows MDMA administration can be rapidly
recovered by the early administration of such an inhibitor.
- Schmidt, C.J., Fadayel, G.M., Sullivan, C.K. and Taylor, V.L.
5-HT2-Receptors Exert a State-Dependent Regulation of Dopaminergic Function -
Studies with MDL-100,907 and the Amphetamine Analogue,
3,4-Methylenedioxymethamphetamine. Eur. J Pharmacol. 223 65-74 (1992).
- The role of serotonin in the stimulation of dopaminergic function as
produced by MDMA, was studied by the use of a selective serotonin receptor
antagonist. The interactions between these receptors and dopamine
activation are discussed.
- Sharkley, J., McBean, D.E. and Kelly, P.A.T. Alterations in Hippocampal
Function Following Repeated Exposure to the Amphetamine Derivative
Methylenedioxymethamphetamine ("Ecstasy"). Psychopharmacology 105 113-118
- Studies with labelled deoxyglucose radiography techniques demonstrate that
the loss of serotonin innervation resulting from MDMA exposure in the rat
resulted in lasting change in hippocampus function.
- Spanos, L.J. and Yamamoto, B.K. Acute and Subchronic Effects of
Methylenedioxymethamphetamine [(+/-) MDMA] on Locomotion and Serotonin
Syndrome Behaviour in the Rat. Pharm. Biochem. Behav. 32 835 (1989).
- The behavioural effects of MDMA on rats were observed. There was a
"serotonin syndrome" (low body posture, forepaw treading, headweaving) as
well as autonomic signs (piloerection and salivation). These were
dose-dependent, and were augmented with sub-acute exposure implying
- Sprouse, J.S., Bradberry, C.W., Roth, R.H. and Aghajanian, G.K. MDMA
3,4-Methylenedioxymeth-amphetamine Inhibits the Firing of Dorsal Raphe
Neurons in Brain Slices via Release of Serotonin. Eur. J. Pharmacol. 167
- Both optical isomers of MDMA as well as p-chloroamphetamine led to a
reversible dose-dependant inhibition of serotonin cell firing. The (+)
isomer was the more potent, and these effects were blocked by Fluoxetine.
It was concluded that MDMA inhibits the raphe neurons through the release
of endogenous serotonin.
- Sprouse, J.S., Bradberry, C.W., Roth, R.H. and Aghajanian, G.K.
3,4-Methylenedioxymethamphetamine-induced Release of Serotonin and
Inhibition of Dorsal Raphe Cell Firing: Potentiation by L-Tryptophane. Eur.
J. Pharmacol. 178 313-320 (1990).
- The relationship between L-tryptophan and the psychotropic and neurotoxic
action of MDMA (in the rat) has been studied. A pretreatment with
tryptophane appeared to increase the potency of MDMA, with the apparent
release of serotonin.
- Steele, T.D., Nichols, D.E. and Yim, G.K. MDMA Transiently Alters Biogenic
Amines and Metabolites in Mouse Brain and Heart. Pharm. Biochem. Behav. 34
- The administration of MDMA to the mouse elevated the brain serotonin levels
(rather than lowering them, as seen in the rat), but had little effect on
the dopamine levels. The highest level depleted norepinephrine in both
brain and heart. Mice appear to be resistant to the neurotoxic effects of
- Stone, D.M., Johnson, M., Hanson, G.R. and Gibb, J.W. Role of Endogenous
Dopamine in the Central Serotonergic Deficits Induced by
3,4-Methylenedioxymethamphetamine. J. Pharm. Exp. Therap. 247 79-87 (1988).
- The role of endogenous dopamine was examined in rats which had been
subjected to both acute and chronic MDMA exposure. Potential mechanisms of
dopamine-mediated toxicity are discussed.
- Thompson, D.M., Winsauer, P.J. and Mastropaolo, J. Effects of
Phencyclidine, Ketamine and MDMA on Complex Operant Behaviour in Monkeys.
Pharm. Biochem. Behav. 26 401-405 (1987).
- The loss of response to conditioned behaviour in monkeys was observed for
the title drugs. All were effective i.m., with phencyclidine being the most
potent, and MDMA being the least potent.
- Winslow, J.T. and Insel, T.R. Serotonergic Modulation of Rat Pup Ultrasonic
Vocal Development: Studies with 3,4-Methylenedioxymethamphetamine.J.
Pharm. Exp. Therap. 254 212-220 (1990).
- New-born rat pups voice a high frequency sound, an isolation call, when
separated from their mothers. These calls were decreased in a
dose-dependant manner following the administration of MDMA. Benzodiazepine
and opioid agonists also show this response. A number of pharmacological
challenges suggest that these effects may be related to serotonin changes.
- Yeh, S.Y. and Hsu, F-L. The Neurochemical and Stimulatory Effects of
Putative Metabolites of 3,4-Methylenedioxyamphetamine and
3,4-Methylenedioxymethamphetamine in Rats. Pharmacol. Biochem. Behav. 39
- Both MDA and MDMA, as well as their metabolites, were injected s.q. into
rats. Brain analyses for serotonin and 5-hydroxyindoleacetic acid were
conducted. Both MDA and MDMA appeared to have a stimulative action of the
- Zacny, J.P., Virus, R.M. and Woolverton, W.L. Tolerance and Cross-Tolerance
to 3,4-Methylenedioxymethamphetamine (MDMA), Methamphetamine and
Methylenedioxyamphetamine. Pharmacol. Biochem. Behav. 35 637-642 (1990).
- Using milk intake as a titrant of behaviour, rats were evaluated for their behavioural responses to MDMA, methamphetamine (MA) and MDA. These animals were then treated chronically with either MDMA or saline, and the degree of tolerance determined by challenges with the three drugs. MDMA produced a tolerance for MDMA, there was some tolerance for these animals to MDA, depending on the schedule established, and there was no tolerance of these animals to the administration of MA.