3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro.
@article{Setola200334methylenedioxymethamphetamine, title={3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro.}, author={Vincent Setola and Sandra J. Hufeisen and Kathryn Jane Grande-Allen and Ivan Vesely and Richard A Glennon and Bruce E. Blough and Richard B. Rothman and Bryan L. Roth}, journal={Molecular pharmacology}, year={2003}, volume={63 6}, pages={ 1223-9 } }
Recent 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…
278 Citations
Serotonin 5-HT2B Receptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT Release In Vivo and In Vitro
- BiologyThe Journal of Neuroscience
- 2008
These findings reveal a novel regulatory component in the actions of MDMA and represent the first demonstration that 5-HT2B receptors play an important role in the brain, i.e., modulation of 5- HT release, and may serve as promising therapeutic drugs for MDMA abuse.
The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats.
- Biology, ChemistryPsychopharmacology
- 2020
Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats, and these data suggest that benzofuran-type compounds may have abuse liability and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.
3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings
- Biology, PsychologyPsychopharmacology
- 2006
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.
Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA).
- BiologyInternational review of neurobiology
- 2009
Cardiovascular toxicity of novel psychoactive drugs: Lessons from the past
- BiologyProgress in Neuro-Psychopharmacology and Biological Psychiatry
- 2012
Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-Methylenedioxymethamphetamine (MDMA) and R(−)-MDMA Trained Mice
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2009
Qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further the understanding of the complex nature of the interoceptive effects of MDMA.
Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms.
- Biology, PsychologyEuropean journal of pharmacology
- 2021
Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers
- Biology, ChemistryJournal of psychoactive drugs
- 2019
MDA induced robust increases in heart rate and blood pressure and increased cortisol and prolactin to a similar degree as MDMA and shared features with MDMA as well as with classical psychedelics, suggesting that the greater duration of MDA effects is due to pharmacodynamics rather than pharmacokinetics.
Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2010
The stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomer might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.
Valvular heart disease in a patient taking 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy').
- MedicineBritish journal of clinical pharmacology
- 2012
This is the first observation of valvular heart disease (VHD) with pathological confirmation related to long term exposure to ecstasy and it is reported that this patient had pulmonary hypertension of 40 mm Hg without right heart failure.
References
SHOWING 1-10 OF 24 REFERENCES
Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.
- Biology, MedicineMolecular pharmacology
- 2000
It is proposed that preferential stimulation of valvular 5-HT(2B) receptors by norfenfluramine, ergot drugs, or5-HT released from carcinoid tumors (with or without accompanying 5- HT(2A) receptor activation) may contribute to valvial fibroplasia in humans.
Evidence for Possible Involvement of 5-HT2B Receptors in the Cardiac Valvulopathy Associated With Fenfluramine and Other Serotonergic Medications
- Medicine, BiologyCirculation
- 2000
It is suggested that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT2B receptors and that clinicians should consider suspending their use of medications with significant activity at5-HT1B receptors.
Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.
- Biology, MedicineBritish journal of clinical pharmacology
- 2000
The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype.
Therapeutic and adverse actions of serotonin transporter substrates.
- BiologyPharmacology & therapeutics
- 2002
Effect of the R(−) and S(+) isomers of MDA and MDMA on phosphotidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors
- Chemistry, BiologyNeuroscience Letters
- 1994
Serotonin Transporters, Serotonin Release, and the Mechanism of Fenfluramine Neurotoxicity
- BiologyAnnals of the New York Academy of Sciences
- 2000
It is hypothesized that dFEN and other amphetamine‐type releasers gain entrance into 5‐HT neurons via interaction with SERTs, and the relevance of this hypothesis for explaining clinical side effects of FEN and dF EN, such as cardiac valvulopathy and primary pulmonary hypertension, warrants further study.
Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension
- Biology, MedicineNature Medicine
- 2002
Using the chronic-hypoxic-mouse model of pulmonary hypertension, it is found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment.
Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells.
- BiologyThe American journal of pathology
- 2002
Serotonin 2B receptor is required for heart development.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 2000
In vivo data suggest that the Gq-coupled receptor 5-HT(2B) uses the signaling pathway of tyrosine kinase receptor ErbB-2 for cardiac differentiation and differentiation of developing and adult heart.
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
- Biology, PsychologyProceedings of the National Academy of Sciences of the United States of America
- 2002
Salvinorin A is the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist for kappa opioid receptors, and may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders).