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The present study aims to evaluate the cardiovascular toxicity and lethality induced by first-generation synthetic cathinones (mephedrone, methylone, and MDPV) and more classical psychostimulants (cocaine and MDMA) in zebrafish embryos using a new approach methodology (NAM). Zebrafish embryos at 4 dpf were exposed to the test drugs for 24 h to identify drug lethality. Drug-induced effects on ventricular and atrial heart rate after 2 h exposure were evaluated, and video recordings were properly analyzed. All illicit drugs displayed similar 24 h LC50 values. Our results indicate that all drugs are able to induce bradycardia, arrhythmia, and atrial-ventricular block (AV block), signs of QT interval prolongation. However, only MDPV induced a different rhythmicity change depending on the chamber and was the most potent bradycardia and AV block-inducing drug compared to the other tested compounds. In summary, our results strongly suggest that the NAM presented in this study can be used for screening NPS for their cardiotoxic effect and especially for their ability to prolong the QT intervals.<\/jats:p>","DOI":"10.3390\/ijms241813869","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:00:52Z","timestamp":1694422852000},"page":"13869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["First-Generation Synthetic Cathinones Produce Arrhythmia in Zebrafish Eleutheroembryos: A New Approach Methodology for New Psychoactive Substances Cardiotoxicity Evaluation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-876X","authenticated-orcid":false,"given":"Elisabet","family":"Teixid\u00f3","sequence":"first","affiliation":[{"name":"GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nutrition and Food Safety, University of Barcelona (INSA-UB), 08921 Santa Coloma de Gramenet, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Riera-Colomer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Pharmacology Section, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-1641","authenticated-orcid":false,"given":"Demetrio","family":"Rald\u00faa","sequence":"additional","affiliation":[{"name":"Institute for Environmental Assessment and Water Research (IDAEA-CSIC), 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-4501","authenticated-orcid":false,"given":"David","family":"Pubill","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Pharmacology Section, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-366X","authenticated-orcid":false,"given":"Elena","family":"Escubedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Pharmacology Section, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Barenys","sequence":"additional","affiliation":[{"name":"GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nutrition and Food Safety, University of Barcelona (INSA-UB), 08921 Santa Coloma de Gramenet, Spain"},{"name":"German Centre for the Protection of Laboratory Animals (Bf3R), German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8904-7398","authenticated-orcid":false,"given":"Raul","family":"L\u00f3pez-Arnau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Pharmacology Section, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/npp.2011.304","article-title":"The Designer Methcathinone Analogs, Mephedrone and Methylone, Are Substrates for Monoamine Transporters in Brain Tissue","volume":"37","author":"Baumann","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00213-013-2967-2","article-title":"Mephedrone and Methylenedioxypyrovalerone (MDPV), Major Constituents of \u201cBath Salts\u201d, Produce Opposite Effects at the Human Dopamine Transporter","volume":"227","author":"Cameron","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/j.bcp.2013.04.004","article-title":"Substituted Methcathinones Differ in Transporter and Receptor Interactions","volume":"85","author":"Eshleman","year":"2013","journal-title":"Biochem. 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