Mephedrene-Induced Cardiac Electrophysiological and Molecular Alterations: An Integrated In Vitro and In Vivo Study
Min Gyeong Kim1,2, Hyun Kyu Min2, Si-Keun Lim1
1Department of Forensic Sciences, Graduate School of Sungkyunkwan University (Natural Sciences Campus), Suwon, South Korea.
Journal of Applied Toxicology : JAT
|May 1, 2026
Summary
Mephedrene, a novel stimulant, significantly harms heart cells and electrical activity in lab tests. In live rats, it caused dangerous QT interval prolongation, indicating serious cardiovascular risks.
Area of Science:
- Pharmacology
- Toxicology
- Cardiology
Background:
- Mephedrene is a novel psychoactive stimulant with unknown cardiotoxic potential.
- Existing stimulants like methamphetamine pose cardiovascular risks.
Purpose of the Study:
- To evaluate the cardiotoxic effects of mephedrene using integrated in vitro and in vivo methods.
- To investigate mephedrene's impact on cardiac electrophysiology, cell viability, and calcium handling.
Main Methods:
- In vitro: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) assessed via multi-electrode array (MEA), WST-1 assay, and Western blotting for SERCA2.
- In vivo: Electrocardiography (ECG) in rats after intravenous mephedrene administration (5 or 15 mg/kg).
Main Results:
- In vitro: Mephedrene reduced hiPSC-CM viability, altered electrophysiological parameters (FPDcF, beat period, spike amplitude), and downregulated SERCA2 expression.
- In vivo: Mephedrene caused dose-dependent QT interval prolongation in rats.
Conclusions:
- Mephedrene induces concentration-dependent cardiac dysfunction, affecting electrophysiology, viability, and calcium handling.
- Findings indicate substantial cardiovascular risk, necessitating toxicological surveillance and regulatory action for novel psychoactive substances.
