3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") Induce
Fenfluramine-Like Proliferative Actions on Human Cardiac Valvular Interstitial Cells in Vitro
Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I,
Glennon RA, Blough B, Rothman RB, Roth BL.
Department of Biochemistry; RM W438,
School of Medicine, Case Western Reserve University,
2109 Adelbert Road, Cleveland, OH 44106-4935.
Mol Pharmacol 2003 Jun;63(6):1223-9
ABSTRACTRecent findings have implicated the 5-hydroxytryptamine 2B (5-HT2B) serotonin receptor in mediating the heart valve fibroplasia [valvular heart disease (VHD)] and primary pulmonary hypertension observed in patients taking the now-banned appetite suppressant fenfluramine (Pondimin, Redux). Via large-scale, random screening of a portion of the receptorome, we have discovered that the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") and its N-demethylated metabolite 3,4-methylenedioxyamphetamine (MDA) each preferentially bind to and activate human recombinant 5-HT2B receptors. We also demonstrate that MDMA and MDA, like fenfluramine and its N-deethylated metabolite norfenfluramine, elicit prolonged mitogenic responses in human valvular interstitial cells via activation of 5-HT2B receptors. We also report that pergolide and dihydroergotamine, two drugs recently demonstrated to induce VHD in humans, potently activate 5-HT2B receptors, thus validating this assay system for its ability to predict medications that might induce VHD. Our discovery that MDMA and a major metabolite, MDA, induce prolonged mitogenic responses in vitro similar to those induced by fenfluramine and norfenfluramine in vivo (i.e., valvular interstitial cell fibroplasia) predict that long-term MDMA use could lead to the development of fenfluramine-like VHD. Because of the widespread abuse of MDMA, these findings have major public health implications. These findings also underscore the necessity of screening current and future drugs at h5-HT2B receptors for agonist actions before their use in humans.Club drugs
Deaths in New York
Long-term brain damage?
Toxic metabolites of MDMA?
Fenfluramine, MDMA and serotonin
A distal axotomy of brain serotonin neurons?
Electrophysiological evidence of 5-HT damage
MDMA (Ecstasy) versus fenfluramine (Pondimin)
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
MDMA (Ecstasy) : neuropharmacology and neurotoxicity
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine
Lack of serotonin neurotoxicity after intracerebral Ecstasy microinjection
and further reading
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family