Abstract

Recently, the number of new psychoactive substances has significantly increased. Despite the systematic introduction of prohibition in trade of medicinal products which mimic the effects of illegal drugs, the problem concerning this group of drugs is still important although knowledge about the mechanism of action of those types of substances is scarce. This study aimed to follow the neurotoxic effect of N-benzylpiperazine (BZP), the central nervous system psychostimulant, using the human cancer LN-18 cell model. The statistically significant elevation of LDH levels, increased mitochondrial membrane potential, decreased ATP and increased ROS production, increased levels of DNA damage marker (8-OHdG) and activation of caspases: -3 and -9 confirmed by Real-Time PCR imply the activation of mitochondrial proapoptotic pathways induced by BZP after 24 h incubation. This study is a novel, preliminary attempt to explain the toxicity of one of the most popular designer drug of abuse at the cellular level.

Highlights

  • N-benzylpiperazine (BZP), known as A2, Legal X, Legal E, or Herbal Highs, is a model compound from the group of new psychoactive compounds

  • The selection of benzylpiperazine concentrations utilized in the experiments was based on a method for evaluating the cytotoxicity of measuring the lactic dehydrogenase (LDH) released into the cells’ culture medium

  • The results presented in this paper indicate that the chosen concentrations of BZP affected the inner mitochondrial membrane potential in the glial cell line LN-18 (Fig. 1)

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Summary

Introduction

N-benzylpiperazine (BZP), known as A2, Legal X, Legal E, or Herbal Highs, is a model compound from the group of new psychoactive compounds. BZP is usually administrated orally in the form of tablets or capsules with different colors, shapes, and logo. The content of a new psychoactive compound in the formulations varies widely and depends mainly on the manufacturer. Average doses of BZP are estimated to be 50–200 mg (Sheridan et al 2007) but there are known reports where a single dose was as high as 2000 mg (Wilkins et al 2008). BZP is often combined with other piperazine derivatives: 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(3-chlorophenyl) piperazine (mCPP), and additives such as caffeine, guarana, or black pepper (Europol– EMCDDA 2007)

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