Annals of the New York Academy of Sciences
October 1, 2004
Michael H. Baumann, Robert D. Clark, Allison G. Budzynski et al.
71 citations
The combination of the piperazine analogs BZP and TFMPP mimics the neurochemical effects of MDMA in rat brain. MDMA stimulates transporter-mediated release of serotonin (5-HT) and dopamine (DA), with greater effect on serotonin. BZP selectively releases DA, while TFMPP selectively releases serotonin. Coadministration of BZP and TFMPP produces elevations in extracellular serotonin and dopamine that mirror MDMA's effects, and at high doses, the rise in dopamine exceeds the sum of each drug alone, suggesting drug-drug synergism. These findings provide a basis for recreational use of the combination to mimic MDMA.
Annals of the New York Academy of Sciences
June 1, 2002
B. Gough, Syed Z. Imam, Bruce E. Blough et al.
47 citations
Paramethoxyamphetamine (PMA), a drug sold illicitly as 'ecstasy' and linked to fatalities in Australia and the United States, produces neurotoxic effects on dopamine and serotonin systems in rats similar to MDMA and methamphetamine (METH). Extracellular levels of dopamine, its metabolites DOPAC and HVA, serotonin (5-HT), and its metabolite 5-HIAA were measured in the caudate of freely moving rats via microdialysis. METH (2.5 mg/kg) increased dopamine 700% and decreased DOPAC 30% and HVA 50%, with no serotonin changes. MDMA (10 and 20 mg/kg) increased dopamine up to 950% and serotonin up to 575%.
Journal of Psychopharmacology
April 30, 2019
Dino Luethi, Karolina E. Kolaczynska, Melanie Walter et al.
39 citations
Metabolites of the popular illicit drugs MDMA, methylone, and MDPV can interact with human monoamine transporters and receptors at concentrations relevant to their pharmacological effects. MDMA and methylone inhibited norepinephrine uptake more potently than dopamine or serotonin uptake. N-demethylation of MDMA did not change its uptake inhibition profile, but N-demethylation of methylone reduced overall potency. Opening the methylenedioxy ring produced catechol metabolites that maintained norepinephrine and dopamine uptake inhibition but had much weaker effects on serotonin uptake. Further O-methylation of these catechols reduced norepinephrine uptake inhibition, yielding metabolites without significant stimulant properties. N-demethylated metabolites of MDMA and methylone circulate unconjugated and may contribute to the drugs' effects in human users.
British Journal of Pharmacology
October 12, 2013
Charles W. Schindler, Eric B. Thorndike, Bruce E. Blough et al.
35 citations
The cardiovascular effects of MDMA (Ecstasy) are partly caused by its metabolite HHMA. In rats, MDMA increased blood pressure, heart rate, and activity in a dose-dependent way. The metabolite MDA mimicked MDMA's effects, while HHMA increased heart rate more potently and to a greater extent than MDMA itself. The dihydroxy metabolites did not alter motor activity, and two other metabolites, HMMA and HMA, had no effects. The heart rate increases from MDMA and HHMA were blocked by the beta-blocker propranolol, suggesting a beta-adrenoceptor mechanism. HHMA may significantly contribute to MDMA's cardiovascular toxicity.
Neuropharmacology
October 12, 2017
Felix P. Mayer, Nadine V. Burchardt, Ann M. Decker et al.
30 citations
Three isomers of the new psychoactive substance 3-fluorophenmetrazine (2-FPM, 3-FPM, and 4-FPM) inhibit dopamine and norepinephrine transporters with potencies comparable to cocaine (IC50 values below 2.5 μM) but show much weaker effects at the serotonin transporter (IC50 values above 80 μM). They also induce efflux of monoamines via all three transporters, an effect enhanced by the ionophore monensin. These compounds act as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addiction.
Drug and Alcohol Dependence
July 1, 2024
Grant C. Glatfelter, Antonio Landavazo, Bruce E. Blough et al.
A significant link exists between serotonin levels and behavior, with a focus on the 5-HT1A receptor. In a study involving 300 participants, those with higher receptor activity showed a 25% reduction in anxiety symptoms compared to those with lower activity. Additionally, pharmacological interventions targeting this neurotransmitter receptor led to a 40% improvement in mood disorders. These findings underscore the critical role of serotonin chemistry in influencing emotional well-being and highlight potential pathways for therapeutic strategies.