First-Generation Synthetic Cathinones Produce Arrhythmia in Zebrafish Eleutheroembryos: A New Approach Methodology for New Psychoactive Substances Cardiotoxicity Evaluation

The increasing number of new psychoactive substances (NPS) entering the illicit drug market, especially synthetic cathinones, as well as the risk of cardiovascular complications, is intensifying the need to quickly assess their cardiotoxic potential. The present study aims to evaluate the cardiovasc...

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Published inInternational journal of molecular sciences Vol. 24; no. 18; p. 13869
Main Authors Teixidó, Elisabet, Riera-Colomer, Clara, Raldúa, Demetrio, Pubill, David, Escubedo, Elena, Barenys, Marta, López-Arnau, Raul
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.09.2023
MDPI
Subjects
Amphetamines
Analysis
Arrhythmia
Cardiac arrhythmia
Cardiotoxicity
Cardiovascular system
Cocaine
Drug dealing
Drug traffic
Drugs
Electrocardiography
Embryos
Heart rate
Methods
new psychoactive substances
Psychotropic drugs
QT-interval
synthetic cathinones
Toxicity
zebrafish
Germany
Spain
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Summary:The increasing number of new psychoactive substances (NPS) entering the illicit drug market, especially synthetic cathinones, as well as the risk of cardiovascular complications, is intensifying the need to quickly assess their cardiotoxic potential. 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.
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These authors contributed equally to this work.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241813869