Cardiovascular Toxicology

, Volume 17, Issue 4, pp 405–416 | Cite as

Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro

  • D. A. FonsecaEmail author
  • A. F. Guerra
  • F. Carvalho
  • E. Fernandes
  • L. M. Ferreira
  • P. S. Branco
  • P. E. Antunes
  • M. J. Antunes
  • M. D. Cotrim
Original Paper


3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a recreational drug used worldwide for its distinctive psychotropic effects. Although important cardiovascular effects, such as increased blood pressure and heart rate, have also been described, the vascular effects of MDMA and metabolites and their correlation with hyperthermia (major side effect of MDMA) are not yet fully understood and have not been previously reported. This study aimed at evaluating the effects of MDMA and its main catechol metabolites, alpha-methyldopamine (α-MeDA), N-methyl-alpha-methyldopamine (N-Me-α-MeDA), 5-(glutathion-S-yl)-alpha-methyldopamine [5-(GSH)-α-MeDA] and 5-(glutathion-S-yl)-N-methyl-alpha-methyldopamine [5-(GSH)-N-Me-α-MeDA], on the 5-HT-dependent vasoactivity in normothermia (37 °C) and hyperthermia (40 °C) of the human internal mammary artery (IMA) in vitro. The results showed the ability of MDMA, α-MeDA and N-Me-α-MeDA to exert vasoconstriction of the IMA which was considerably higher in hyperthermic conditions (about fourfold for MDMA and α-MeDA and twofold for N-Me-α-MeDA). The results also showed that all the compounds may influence the 5-HT-mediated concentration-dependent response of IMA, as MDMA, α-MeDA and N-Me-α-MeDA behaved as partial agonists and 5-(GSH)-α-MeDA and 5-(GSH)-N-Me-α-MeDA as antagonists. In conclusion, MDMA abuse may imply a higher cardiovascular risk associated both to MDMA and its metabolites that might be relevant in patients with underlying cardiovascular diseases, particularly in hyperthermia.


3,4-Methylenedioxymethamphetamine MDMA Catecholic metabolites of MDMA 5-Hydroxytryptamine Vascular effects Hyperthermia Human internal mammary artery 



The authors acknowledge all the support and help in the collection of samples from the nurses of Cardiothoracic Surgery, University Hospital of Coimbra.

Compliance with ethical standards

Conflicts of interest

The authors report no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • D. A. Fonseca
    • 1
    • 2
    • 3
    Email author
  • A. F. Guerra
    • 1
  • F. Carvalho
    • 4
  • E. Fernandes
    • 5
  • L. M. Ferreira
    • 6
  • P. S. Branco
    • 6
  • P. E. Antunes
    • 7
  • M. J. Antunes
    • 7
  • M. D. Cotrim
    • 1
    • 2
    • 3
  1. 1.Pharmacology and Pharmaceutical Care Group, Faculty of PharmacyUniversity of CoimbraCoimbraPortugal
  2. 2.Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of MedicineUniversity of CoimbraCoimbraPortugal
  3. 3.CNC.IBILIUniversity of CoimbraCoimbraPortugal
  4. 4.UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal
  5. 5.UCIBIO/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal
  6. 6.REQUIMTE/CQFB (Centro de Química Fina e Biotecnologia), Department of Chemistry, Faculty of Sciences and TechnologyUniversity Nova of LisbonCaparicaPortugal
  7. 7.Center of Cardiothoracic SurgeryCoimbra University HospitalsCoimbraPortugal

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