Genotoxicity Evaluation of The Novel Psychoactive Substance MTTA

Int J Mol Sci. 2023 Jun 22;24(13):10498. doi: 10.3390/ijms241310498.

Abstract

MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test". To consider the in vitro effects of both the parental compound and the related metabolites, TK6 cells were treated with MTTA in the absence or presence of an exogenous metabolic activation system (S9 mix) for a short-term time (3 h) followed by a recovery period (23 h). No statistically significant increase in the MNi frequency was detected. Specifically, in the presence of S9 mix, only a slight increasing trend was observable at all tested concentrations, whereas, without S9 mix, at 75 µM, almost a doubling of the negative control was reached. For the purposes of comprehensive evaluation, a long-term treatment (26 h) was also included. In this case, a statistically significant enhancement in the MNi frequency was observed at 50 µM.

Keywords: MTTA; cathinones; flow cytometry; genotoxicity; in vitro mammalian cell micronucleus test; mephtetramine; novel psychoactive substances; stimulant.

MeSH terms

  • Animals
  • Central Nervous System Agents
  • DNA Damage*
  • Mammals / metabolism
  • Micronucleus Tests / methods
  • Mutagenicity Tests / methods
  • Mutagens* / metabolism
  • Mutagens* / toxicity

Substances

  • Mutagens
  • (5-methoxy-2-thienyl)thioacetic acid
  • mephtetramine
  • Central Nervous System Agents