Monoaminergic toxicity induced by cathinone phthalimide: An in vitro study

[Display omitted] •Cathinone phthalimide (CP) increases cell death beginning at 10μM.•CP does not affect glutathione, suggesting toxicity may not be from oxidative stress.•CP alters dopamine and serotonin levels, similar to mephedrone or methylone. Bath salts, or synthetic cathinones, have cocaine-l...

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Bibliographic Details
Published in:Neuroscience letters 2017-08, Vol.655, p.76-81
Main Authors: Lantz, Susan M., Rosas-Hernandez, Hector, Cuevas, Elvis, Robinson, Bonnie, Rice, Kenner C., Fantegrossi, William E., Imam, Syed Z., Paule, Merle G., Ali, Syed F.
Format: Article
Language:English
Subjects:
Animals
Bath salt
Cathinone phthalimide
Cell Death - drug effects
Central Nervous System Stimulants - toxicity
Dopamine
Dopamine - metabolism
Glutathione - metabolism
Mephedrone
Methylone
Mitochondria - drug effects
Mitochondria - physiology
PC12 Cells
Phthalimides - toxicity
Propiophenones - toxicity
Rats
Serotonin
Serotonin - metabolism
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Summary:[Display omitted] •Cathinone phthalimide (CP) increases cell death beginning at 10μM.•CP does not affect glutathione, suggesting toxicity may not be from oxidative stress.•CP alters dopamine and serotonin levels, similar to mephedrone or methylone. Bath salts, or synthetic cathinones, have cocaine-like or amphetamine-like properties and induce psychoactive effects via their capacity to modulate serotonin (5-HT) and dopamine (DA). Structurally distinct synthetic cathinones are continuously being generated to skirt existing drug laws. One example of these modified compounds is cathinone phthalimide (CP), which has already appeared on the global market. The lack of toxicological studies on the effects of CP on monoaminergic systems led to the development of the present study in order to generate an acute toxicity profile for CP, and to clarify whether it primarily affects both dopamine and serotonin, like the synthetic cathinones mephedrone and methylone, or primarily affects dopamine, like 3, 4-methylenedioxypyrovalerone (MDPV). For the first time, the toxicity profile of CP (10μM–1000μM) is reported. In pheochromocytoma cells, exposure to CP induced cell death, and altered mitochondrial function, as well as intracellular DA and 5-HT levels; at the same time, reduced glutathione (GSH) levels remained unaffected. This seems to indicate that CP functions like mephedrone or methylone. The role of CP metabolites, the effect of CP induced hyperthermia on neurotoxicity, and its ability to traverse the blood-brain barrier warrant further consideration.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2017.06.059