N-Substituted Piperazines Abused by Humans Mimic the Molecular Mechanism of 3,4-Methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’)

  title={N-Substituted Piperazines Abused by Humans Mimic the Molecular Mechanism of 3,4-Methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’)},
  author={Michael H Baumann and Robert D. Clark and Allison G Budzynski and John S. Partilla and Bruce E. Blough and Richard B. Rothman},
3,4-Methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’) is an illicit drug that stimulates the release of serotonin (5-HT) and dopamine (DA) from neurons. Recent evidence reveals that drug users are ingesting piperazine analogs, like 1-benzylpiperazine (BZP, or ‘A2’) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, or ‘Molly’), to mimic psychoactive effects of MDMA. In the present study, we compared the neurochemistry of MDMA, BZP, and TFMPP in rats. The effects of MDMA, BZP, and TFMPP on… 
3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings
MDMA-induced 5- HT depletions are not necessarily synonymous with neurotoxic damage, however, doses of MDMA which do not cause long-term 5-HT depletion can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.
Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine.
In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity, suggesting the involvement ofVMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA.
Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives.
Effect of N-Benzylpiperazine, Its Metabolite N-Benzylethylenediamine, and Its Disubstituted Analogue N,N'-Dibenzylpiperazine on the Acquisition, Formation, and Consolidation of Memory in Mice
BZP, its metabolite BEDA, and the disubstituted analogue DBZP enhance the memory and show anxiogenic effects, which represent new psychoactive compounds with the potential to be new BZP-like recreational entities.
Dissociative and sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-benzylpiperzine (BZP)
This is the first case series of confirmed toxicity associated with recreational use of TFMPP in combination with BZP, with clinical features not consistent with BzP toxicity.
Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA).
Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence
Increase in knowledge of the neurochemical substrates of the rewarding effects of MDMA may contribute to the design of new pharmacological treatments for individuals who develop MDMA dependence.
Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice
Evidence is provided that long-term caffeine administration has a powerful influence on functions of dopaminergic and serotonergic neurons in the mouse brain and on neurotoxic effects evoked by MDMA.


3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions.
Evidence is summarized to suggest that the influence of 5-HT receptors on behavioral function is dependent upon the specific neurochemical environment evoked by a given drug, specifically discussed here with regard to the interaction between 5- HT and DA systems.
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users.
Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats.
It is suggested that (+)MDMA increases locomotor activity via mechanisms that are dependent on the release of central 5-HT and that are qualitatively different from the mechanism of action of (+)amphetamine.
Effects of certain hallucinogenic amphetamine analogues on the release of [3H]serotonin from rat brain synaptosomes.
The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their alpha, alpha-dimethylated derivatives, were evaluated for an effect on the release of [3H]serotonin from rat whole brain synaptosomes and suggested that transmitter release may play a role in the biological activity of MDMA.
Chemistry, Pharmacology, Toxicology, and Hepatic Metabolism of Designer Drugs of the Amphetamine (Ecstasy), Piperazine, and Pyrrolidinophenone Types: A Synopsis
Abstract: Designer drugs of the amphetamine type (eg, MDMA, MDEA, MDA), of the new benzyl or phenyl piperazine type (eg, BZP, MDBP, mCPP, TFMPP, MeOPP), or of the pyrrolidinophenone type (eg, PPP,