Contractile effects of 3,4-methylenedioxymethamphetamine on the human internal mammary artery

- The effects of MDMA in the human internal mammary artery were evaluated.
- Vascular rings were prepared for isometric contractions.
- MDMA has an agonistic effect independent of SERT and mediated by 5-HT2A receptors.
- MDMA shifted the 5-HT CR curve to the right with no reduction of the maximum effect.
- These effects can explain the cardiovascular risk profile of this psychostimulant.

Since the late 1980s numerous reports have detailed adverse reactions to the use of 3,4-methylenedioxymethamphetamine (MDMA) associated with cardiovascular collapse and sudden death, following ventricular tachycardia and hypertension. For a better understanding of the effects of MDMA on the cardiovascular system, it is critical to determine their effects at the vasculature level, including the transporter or neurotransmitter systems that are most affected at the whole range of drug doses. With this purpose in mind, the aim of our study was to evaluate the contractile effect of MDMA in the human internal mammary artery, the contribution of SERT for this effect and the responsiveness of this artery to 5-HT in the presence of MDMA. We have also studied the possible involvement of 5-HT2 receptors on the MDMA contractile effect in this human blood vessel using ketanserin. Our results showed that MDMA contracted the studied human's internal mammary artery in a SERT-independent form, through activation of 5-HT2A receptors. Considering the high plasma concentrations achieved in heavy users or in situations of acute exposure to drugs, this effect is probably involved in the cardiovascular risk profile of this psychostimulant, especially in subjects with pre-existing cardiovascular disease.