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.
Cardiovasc Toxicol. 2017 Oct;17(4):405-416. doi: 10.1007/s12012-017-9398-y.
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.
3,4-亚甲二氧基甲基苯丙胺（MDMA 或“摇头丸”）是一种在全球范围内被滥用的娱乐性药物，因其具有独特的精神活性作用。虽然已经描述了重要的心血管作用，如血压和心率升高，但 MDMA 及其代谢物的血管作用及其与体温升高（MDMA 的主要副作用）的相关性尚未完全阐明，以前也没有报道过。本研究旨在评估 MDMA 及其主要儿茶酚代谢物，α-甲基多巴胺（α-MeDA）、N-甲基-α-甲基多巴胺（N-Me-α-MeDA）、5-（谷胱甘肽-S- 基）-α-甲基多巴胺[5-（GSH）-α-MeDA]和 5-（谷胱甘肽-S-基）-N-甲基-α-甲基多巴胺[5-（GSH）-N-Me-α-MeDA]对正常体温（37°C）和体温升高（40°C）下人体内乳动脉（IMA）5-HT 依赖性血管活性的影响。结果表明，MDMA、α-MeDA 和 N-Me-α-MeDA 具有收缩 IMA 的能力，在体温升高的情况下，这种收缩作用明显增强（MDMA 和 α-MeDA 约增加四倍，N-Me-α-MeDA 增加两倍）。结果还表明，所有化合物可能影响 IMA 的 5-HT 介导的浓度依赖性反应，因为 MDMA、α-MeDA 和 N-Me-α-MeDA 表现为部分激动剂，而 5-（GSH）-α-MeDA 和 5-（GSH）-N-Me-α-MeDA 表现为拮抗剂。总之，MDMA 滥用可能意味着与 MDMA 及其代谢物相关的心血管风险更高，这可能与患有潜在心血管疾病的患者相关，特别是在体温升高的情况下。
