title: Contractile effects of 3,4-methylenedioxymethamphetamine on the human internal mammary artery.
abstract: 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.
authors.affiliation: Group of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Portugal. Electronic address: sonias@ci.uc.pt.
authors.forename: Sónia
authors.initials: S
authors.lastname: Silva
authors.affiliation: UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: UCIBIO-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemistry, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.affiliation: Cardiothoracic Surgery, University Hospital of Coimbra, Coimbra, Portugal.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Antunes
authors.affiliation: Group of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Portugal.
authors.forename: Maria Dulce
authors.initials: MD
authors.lastname: Cotrim
mesh_terms: D005473:Fluoxetine / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D005473:Fluoxetine; D006213:Hallucinogens; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human
keywords: 5-HT; Fluoxetine; Human internal mammary artery; Ketanserin; MDMA (ecstasy)