title: Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro.
abstract: 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.
authors.affiliation: Pharmacology and Pharmaceutical Care Group, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal. diogo.andre.fonseca@gmail.com.|Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal. diogo.andre.fonseca@gmail.com.|CNC.IBILI, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal. diogo.andre.fonseca@gmail.com.
authors.forename: D A
authors.initials: DA
authors.lastname: Fonseca
authors.affiliation: Pharmacology and Pharmaceutical Care Group, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Guerra
authors.affiliation: UCIBIO/REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313, Porto, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: UCIBIO/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313, Porto, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Fernandes
authors.affiliation: REQUIMTE/CQFB (Centro de Química Fina e Biotecnologia), Department of Chemistry, Faculty of Sciences and Technology, University Nova of Lisbon, Quinta da Torre, 2829-516, Caparica, Portugal.
authors.forename: L M
authors.initials: LM
authors.lastname: Ferreira
authors.affiliation: REQUIMTE/CQFB (Centro de Química Fina e Biotecnologia), Department of Chemistry, Faculty of Sciences and Technology, University Nova of Lisbon, Quinta da Torre, 2829-516, Caparica, Portugal.
authors.forename: P S
authors.initials: PS
authors.lastname: Branco
authors.affiliation: Center of Cardiothoracic Surgery, Coimbra University Hospitals, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: P E
authors.initials: PE
authors.lastname: Antunes
authors.affiliation: Center of Cardiothoracic Surgery, Coimbra University Hospitals, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: M J
authors.initials: MJ
authors.lastname: Antunes
authors.affiliation: Pharmacology and Pharmaceutical Care Group, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.|Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.|CNC.IBILI, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal.
authors.forename: M D
authors.initials: MD
authors.lastname: Cotrim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism* / Q000633:toxicity*; D009924:Organ Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: 3,4-Methylenedioxymethamphetamine; 5-Hydroxytryptamine; Catecholic metabolites of MDMA; Human internal mammary artery; Hyperthermia; MDMA; Vascular effects