Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Abstract

Synthetic opioids are gaining more and more popularity among recreational users as well as regular abusers. One of such novel psychoactive substance, is etazene, which is the most popular opioid drug in the darknet market nowadays. Due to limited information available concerning its activity, we aimed to characterize its developmental toxicity, including cardiotoxicity with the use of in vivo Danio rerio and in silico tools. Moreover, we aimed, for the first time, to characterize the metabolite of etazene, which could become a potential marker of its use for future forensic analysis. The results of our study proved severe dose-dependent developmental toxicity of etazene (applied concentrations 10–300 µM), including an increase in mortality, developmental malformations, and serious cardiotoxic effects, as compared with well-known and used opioid—morphine (applied concentrations 1–50 mM). In silico findings indicate the high toxic potential of etazene which may lead to drug-drug interactions and accumulation of substances. Furthermore, phase I metabolite of etazene resulting from N-dealkylation reaction was identified, and therefore it should be considered as a target for toxicological screening. Nonetheless, the exact mechanism of observed effects in response to etazene should be further examined.