Zebrafish embryo-larval testing reveals differential toxicity of new psychoactive substances.
Toxicology reports June 1, 2025 Leonardo Costalonga Rodrigues, Alexandre Barcia de Godoi, Viviane Cristina Fais et al. 4 citations
MDMB-4en-PINACA, a synthetic cannabinoid receptor agonist, caused severe developmental abnormalities and high embryo mortality in zebrafish at 10 µM, including pericardial edema, yolk edema, coagulation, and lack of heartbeat or somite formation. In contrast, the ketamine derivatives deschloroketamine and 2-fluorodeschloroketamine showed low embryo mortality even at higher concentrations. In larval stages, MDMB-4en-PINACA caused 8% mortality at 10 µM by eight days post-fertilization, while the ketamine derivatives led to 100% mortality at 2000 µM. MDMB-4en-PINACA was approximately 26 times more toxic than the ketamine derivatives based on LC50 values. The results support the absence of NMDA receptors in early zebrafish life stages, explaining the lower toxicity of ketamine derivatives early on.