Molecular mechanism of action and safety of 5-(3-chlorophenyl)-4-hexyl-2,4-dihydro-3 H-1,2,4-triazole-3-thione - a novel anticonvulsant drug candidate

Int J Med Sci. 2017 Jul 18;14(8):741-749. doi: 10.7150/ijms.20001. eCollection 2017.

Abstract

Previously, it was found that 5-(3-chlorophenyl)-4-hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP-315) effectively protects mice from maximal electroshock-induced seizures. The aim of this study was to determine possible interactions between TP-315 and different molecular targets, i.e. GABAA receptors, voltage-gated sodium channels, and human neuronal α7 and α4β2 nicotinic acetylcholine receptors. The influence of TP-315 on the viability of human hepatic HepG2 cells was also established using PrestoBlue and ToxiLight assays. It was found that the anticonvulsant activity of TP-315 results (at least partially) from its influence on voltage-gated sodium channels (VGSCs). Moreover, the title compound slightly affected the viability of human hepatic cells.

Keywords: Sodium channels; [3H]-batrachotoxin; cell viability assays.; patch-clamp.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage*
  • Disease Models, Animal
  • Electroshock / adverse effects
  • Hep G2 Cells
  • Humans
  • Mice
  • Patch-Clamp Techniques
  • Seizures / drug therapy*
  • Seizures / genetics
  • Seizures / pathology
  • Thiones / administration & dosage*
  • Triazoles / administration & dosage
  • Voltage-Gated Sodium Channels / drug effects
  • Voltage-Gated Sodium Channels / genetics*

Substances

  • Anticonvulsants
  • Thiones
  • Triazoles
  • Voltage-Gated Sodium Channels
  • 1,2,4-triazole