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

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.