PLoS ONE
May 4, 2012
Cédric M. Hysek, Linda D. Simmler, V.g. Nicola et al.
158 citations
Taking the antidepressant duloxetine before MDMA (ecstasy) blocks many of the drug's effects. In a controlled experiment with 16 healthy volunteers, duloxetine prevented MDMA from raising blood pressure, heart rate, and norepinephrine levels, and also reduced the subjective drug experience. This happened even though duloxetine increased MDMA concentrations in the blood. Laboratory tests on human cells confirmed that duloxetine stops MDMA from releasing the neurotransmitters serotonin and norepinephrine. These findings indicate that MDMA's psychological effects depend on its ability to release both serotonin and norepinephrine, and suggest duloxetine could help treat dependence on stimulant drugs.
Frontiers in Pharmacology
April 24, 2019
Dino Luethi, Melanie Walter, Xun Zhou et al.
33 citations
Halogenated derivatives of amphetamine-type stimulants, such as 4-fluoroamphetamine and 4-chloroamphetamine, inhibit the norepinephrine transporter at submicromolar concentrations and the dopamine transporter at low micromolar concentrations. As the size of the para-substituent increases, selectivity shifts from dopamine to serotonin transporter inhibition, resulting in potent serotonin uptake inhibition. All tested compounds deplete cellular ATP at lower concentrations (0.25–2 mM) than they cause cell membrane integrity loss (≥0.5 mM), indicating mitochondrial toxicity. The toxicity rank order for para-substituents is chloride > fluoride > hydrogen. Para-halogenation increases the risk of serotonergic neurotoxicity and may heighten hepatic toxicity through mitochondrial impairment.
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.