Are Designer Drugs Putting Your Heart at Risk? A Comparative Study of Methylone and 3,4-DMMC

Abstract

Background: Synthetic cathinones (SC) have emerged as a new class of recreational psychoactive substances with pharmacological properties similar to those of traditional amphetamines [1]. These substances appear to be involved in a range of cardiac events, including myocardial infarction and sudden cardiac death due to fatal arrhythmias [2]. However, the mechanisms underlying SC-induced cardiotoxicity remain unclear.
Objective: The aim of this study was to investigate the cardiotoxicity of methylone and 3,4-dimethylmethcathinone (3,4-DMMC) in vitro using the rat cardiomyocyte cell line H9c2.
Methods: Non-differentiated H9c2 cells were exposed to methylone (0.1 to 4.0 mM) and 3,4-DMMC (0.01 to 1.0 mM) for 24 hours. Cell viability was assessed by the 3-(4,5-dimethyiazol-2-1)-2-5-diphenyl tetrazolium bromide (MTT) assay. The role of oxidative stress was assessed by the production of reactive oxygen and nitrogen species (ROS/RNS), measured from 0.5 to 24 h, at the EC10 and EC50 concentrations of both SC.
Results: Both methylone and 3,4-DMMC induced a concentration-dependent decrease in cell viability after 24 hours. 3,4-DMMC was found to be significantly more toxic than methylone, with its concentration-response curve located further to the left. This result was supported by EC50 values of 0.178 mM for 3,4-DMMC and 1.569 mM for methylone, p <0.0001. ROS/RNS production increased in a concentration- and time-dependent manner, indicating an overall increase in oxidative stress over time. Methylone produced a higher fold increase in ROS/RNS than 3,4-DMMC at both EC10 (4.1-fold versus 2.7-fold increase respectively, p <0.0001) and EC50 (4.8-fold versus 3.8-fold increase respectively, p=0.0124).
Conclusions: Our results support that SC have associated cardiotoxicity, with 3,4-DMMC being more toxic than methylone in terms of cell death, while methylone seems to contribute more significantly to oxidative stress. Further research is being carried out to investigate the potential protective effect of antioxidants against these SC, which may be useful in the future to treat poisoning caused by these drugs.