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MDMA modulates 5-HT1-mediated contractile response of the human internal thoracic artery in vitro

Diogo A Fonseca1, Cristina Teixeira2, Félix Carvalho3

  • 1Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC.iCBR, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|November 19, 2018
PubMed

Insights

3,4-Methylenedioxymethamphetamine (MDMA) affects blood pressure and heart rate by interacting with serotonin (5-HT) receptors. This study shows MDMA influences 5-HT receptor agonists, impacting vascular responses.

Area of Science:

  • Pharmacology
  • Cardiovascular Science
  • Neuroscience

Background:

  • 3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug known for psychotropic and cardiovascular effects.
  • MDMA acts as a partial agonist on 5-hydroxytryptamine (5-HT) receptors, specifically 5-HT2A, in human internal thoracic artery.
  • Understanding MDMA's interaction with various 5-HT receptor subtypes is crucial for explaining its vascular effects.

Purpose of the Study:

  • To investigate the interaction of MDMA with 5-HT receptor agonists.
  • To determine how MDMA influences the activity of 5-carboxamidotryptamine (5-CT) and sumatriptan at 5-HT receptors.
  • To elucidate the role of 5-HT receptor affinity in MDMA-induced vascular effects.

Main Methods:

  • In vitro study using human internal thoracic artery.
  • Testing MDMA at concentrations of 400, 800, and 1600 μM.
  • Assessing the effects of MDMA on concentration-dependent responses to 5-CT and sumatriptan.

Main Results:

  • MDMA significantly reduced the concentration-dependent response of 5-CT (up to 97.3%) and sumatriptan (up to 72.43%) at 1600 μM.
  • A lower concentration of MDMA (400 μM) potentiated the response to sumatriptan.
  • These findings suggest MDMA interacts with 5-HT receptor activation, particularly the 5-HT1 subtype, in peripheral vasculature.

Conclusions:

  • MDMA's affinity for 5-HT receptors plays a significant role in its vascular effects.
  • The study supports the hypothesis that MDMA's interaction with 5-HT1 receptors contributes to its cardiovascular impact.
  • Further research into MDMA-5-HT receptor interactions is warranted to understand its full physiological consequences.
Keywords:
3,4-Methylenedioxymethamphetamine5-HT(1) receptorsHuman internal thoracic arteryMDMASumatriptanVascular effects

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