Monoaminergic toxicity induced by cathinone phthalimide: An in vitro study. (10th August 2017)

• Record Type: Journal Article
• 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.
• Is Part Of: Neuroscience letters. Volume 655(2017)
• Page Start: 76
• Page End: 81
• Publication Date: 2017-08-10
• Subjects: METH methamphetamine -- DA dopamine -- 5-HT serotonin -- MDPV 3 4-methylenedioxypyrovalerone -- CP cathinone phthalimide -- PMS phenazine methosulfate -- LDH lactate dehydrogenase -- GSH glutathione -- XTT 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide; Bath salt -- Cathinone phthalimide -- Dopamine -- Serotonin -- Methylone -- Mephedrone; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.06.059
• Languages: English
• ISSNs: 0304-3940

Abstract

Graphical abstract: Highlights: Cathinone phthalimide (CP) increases cell death beginning at 10 μM. CP does not affect glutathione, suggesting toxicity may not be from oxidative stress. CP alters dopamine and serotonin levels, similar to mephedrone or methylone. Abstract: 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 (10 μM–1000 μM) 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.