Mephedrene-Induced Cardiac Electrophysiological and Molecular Alterations: An Integrated In Vitro and In Vivo Study

Mephedrene-Induced Cardiac Electrophysiological and Molecular Alterations: An Integrated In Vitro and In Vivo Study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 24 September 2025 V1 Latest version Share on Mephedrene-Induced Cardiac Electrophysiological and Molecular Alterations: An Integrated In Vitro and In Vivo Study Authors : Min Gyeong Kim 0009-0002-8275-8386 , Hyun Kyu Min , Si-Keun Lim [email protected] , and Ki Kyung Jung Authors Info & Affiliations https://doi.org/10.22541/au.175871385.58305780/v1 Published Journal of Applied Toxicology Version of record Peer review timeline 172 views 114 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background Mephedrene, a psychoactive stimulant structurally related to methamphetamine, has recently emerged on illicit markets. Although methamphetamine-like compounds are known to stimulate the central nervous system and elevate cardiovascular risk, the pharmacological and toxicological characteristics of mephedrene, particularly its cardiotoxic potential, are poorly defined. Methods Cardiotoxicity was evaluated using integrated in vitro and in vivo approaches. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were assessed for electrophysiological alterations by multi-electrode array (MEA) recordings, cell viability by WST-1 assay, and sarco/endoplasmic reticulum Ca 2+ -ATPase 2 (SERCA2) expression by Western blotting. In vivo electrocardiography (ECG) was recorded in rats following intravenous mephedrene administration (5 or 15 mg/kg). Results WST-1 assays revealed a significant decline in cell viability from 300 µM. MEA analysis showed reductions in Fridericia-corrected field potential duration (FPDcF) and beat period at 10 µM, and a decrease in spike amplitude at 50 µM. Western blots demonstrated SERCA2 downregulation at 50 and 100 µM, consistent with impaired Ca 2+ handling. In vivo, mephedrene produced significant QT interval prolongation at 5 and 15 mg/kg, with a dose-dependent increase. Conclusion This study provides the first integrated evidence that mephedrene induces concentration-dependent disturbances in cardiac electrophysiology, viability, and Ca 2+ -regulatory mechanisms in vitro, and prolongs QT intervals in vivo. These findings indicate substantial cardiovascular risk associated with mephedrene exposure and underscore the need for toxicological surveillance and regulatory action to mitigate potential public health harms posed by emerging novel psychoactive substances. Supplementary Material File (mephedrene-induced cardiac electrophysiological and molecular alterations an integrated in vitro and in vivo study_.docx) Download 1.86 MB Information & Authors Information Version history V1 Version 1 24 September 2025 Peer review timeline Published Journal of Applied Toxicology Version of Record 1 May 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords basic: cellular electrophysiology/electropharmocology basic: ion channels and membrane transporters basic: molecular biology/genetics Authors Affiliations Min Gyeong Kim 0009-0002-8275-8386 Sungkyunkwan University View all articles by this author Hyun Kyu Min Ministry of Food and Drug Safety View all articles by this author Si-Keun Lim [email protected] Sungkyunkwan University View all articles by this author Ki Kyung Jung Ministry of Food and Drug Safety View all articles by this author Metrics & Citations Metrics Article Usage 172 views 114 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Min Gyeong Kim, Hyun Kyu Min, Si-Keun Lim, et al. Mephedrene-Induced Cardiac Electrophysiological and Molecular Alterations: An Integrated In Vitro and In Vivo Study. Authorea . 24 September 2025. DOI: https://doi.org/10.22541/au.175871385.58305780/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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