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

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. GABA(A) rec...

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Detalles Bibliográficos
Autores principales: Kaproń, Barbara, Łuszczki, Jarogniew, Paneth, Agata, Wujec, Monika, Siwek, Agata, Karcz, Tadeusz, Mordyl, Barbara, Głuch-Lutwin, Monika, Gryboś, Anna, Nowak, Gabriel, Pająk, Karolina, Jóźwiak, Krzysztof, Tomczykowski, Adam, Plech, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562128/
https://www.ncbi.nlm.nih.gov/pubmed/28824309
http://dx.doi.org/10.7150/ijms.20001
Descripción
Sumario: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. GABA(A) 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.

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