Title:Neurotoxicity Induced by Mephedrone: An up-to-date Review
Volume: 15
Issue: 5
Author(s): Flaminia Pantano, Roberta Tittarelli, Giulio Mannocchi, Roberta Pacifici, Alessandro di Luca, Francesco Paolo Busardò*Enrico Marinelli
Affiliation:
- Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University, Viale Regina Elena 336, 00161 Rome, Italy,Italy
Keywords:
Mephedrone, neurotoxicity, neuropharmacology, monoamine transporters, 5HT, DA.
Abstract: Background: Mephedrone is a β-ketoamphetamine belonging to the family of synthetic
cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant
properties as well as for their abuse potential.
Objective: The aim of this review was to examine the emerging scientific literature on the possible
mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental
studies, mainly carried on animal models.
Materials and Methods: Relevant scientific articles were identified from international literature
databases (Medline, Scopus, etc.) using the keywords: “Mephedrone”, “4-MMC,” “neurotoxicity,”
“neuropharmacology”, “patents”, “monoamine transporters” and “neurochemical effects”.
Results: Of the 498 sources initially found, only 36 papers were suitable for the review. Neurotoxic
effect of mephedrone on 5-hydroxytryptamine (5-HT) and dopamine (DA) systems remains
controversial. Although some studies in animal models reported no damage to DA nerve endings in
the striatum and no significant changes in brain monoamine levels, some others suggested a rapid
reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after
binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve
endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex
lipid peroxidation were also reported. In vitro cytotoxic properties were also observed, suggesting
that mephedrone may act as a reductant agent and can also determine changes in mitochondrial
respiration. However, due to the differences in the design of the experiments, including temperature
and animal model used, the results are difficult to compare.
Conclusions: Further studies on toxicology and pharmacology of mephedrone are therefore necessary
to establish an appropriate treatment for substance abuse and eventual consequences for public health
