Monoaminergic toxicity induced by cathinone phthalimide: An in vitro study

Neurosci Lett. 2017 Aug 10:655:76-81. doi: 10.1016/j.neulet.2017.06.059. Epub 2017 Jul 3.

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 (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.

Keywords: Bath salt; Cathinone phthalimide; Dopamine; Mephedrone; Methylone; Serotonin.

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Central Nervous System Stimulants / toxicity*
  • Dopamine / metabolism*
  • Glutathione / metabolism
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • PC12 Cells
  • Phthalimides / toxicity*
  • Propiophenones / toxicity*
  • Rats
  • Serotonin / metabolism*

Substances

  • Central Nervous System Stimulants
  • Phthalimides
  • Propiophenones
  • cathinone phthalimide
  • Serotonin
  • Glutathione
  • Dopamine