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

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a popular recreational drug of abuse. In addition to its characteristic psychotropic effects, important cardiovascular effects have been described such as increased blood pressure and heart rate. MDMA was previously shown to behave as a partial agonist on 5-hydroxytryptamine (5-HT) receptors in the human internal thoracic artery in vitro, involving the 5-HT2A subtype. Here, we studied the interaction of MDMA (400, 800 and 1600 mu m) with the following 5-HT receptor agonists: 5-carboxamidotryptamine (5-CT, full agonist for the 5-FIT1, 5-HT2, 5-HT5, 5-HT6 and 5-HT7 receptors) and sumatriptan (selective 5-HT1B/1D receptors agonist). The results showed the ability of MDMA to influence the concentration-dependent response of 5-CT (97.3% of maximal reduction for 1600 mu M of MDMA) and sumatriptan (72.43% of maximal reduction for 1600 mu M of MDMA). The lower concentration of MDMA (400 mu M) produced a significant potentiation of the response to sumatriptan thus suggesting an interaction of MDMA with the activation of 5-HT receptors, namely of the 5-HT1 subtype, in the peripheral vasculature. Together our results further support the importance of the affinity of MDMA to 5-HT receptors in the vascular effects of this drug.