Para-Halogenation of Amphetamine and Methcathinone Increases the Mitochondrial Toxicity in Undifferentiated and Differentiated SH-SY5Y Cells
International Journal of Molecular Sciences April 18, 2020 Xun Zhou, Jamal Bouitbir, Matthias E. Liechti et al. 29 citations
Halogenating amphetamines and methcathinones at the para position increases their neurotoxic properties. In lab-grown SH-SY5Y cells, 4-fluoroamphetamine (4-FA), 4-chloroamphetamine (PCA), and 4-chloromethcathinone (4-CMC) reduced cellular energy (ATP) and damaged plasma membranes, with differentiated cells less sensitive than undifferentiated ones. The order of toxicity was chloride > fluoride > hydrogen for both drug families. These compounds also lowered mitochondrial membrane potential, disrupted the electron transport chain, raised reactive oxygen species, and triggered apoptosis via the intrinsic pathway. Although the toxic concentrations exceeded those needed for psychoactive effects, the findings raise concerns about uncontrolled recreational use of these designer drugs.