International Journal of Medical Sciences

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23 October 2017

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

Research Paper

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

Barbara Kaproń1, Jarogniew Łuszczki2, 3, Agata Paneth1, Monika Wujec1, Agata Siwek4, Tadeusz Karcz5, Barbara Mordyl4, Monika Głuch-Lutwin4, Anna Gryboś4, Gabriel Nowak4, Karolina Pająk6, Krzysztof Jóźwiak6, Adam Tomczykowski1, Tomasz Plech7✉

1. Department of Organic Chemistry, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland;
2. Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, Lublin 20-090, Poland;
3. Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, Lublin 20-950, Poland;
4. Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland;
5. Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland;
6. Department of Biopharmacy, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland;
7. Department of Pharmacology, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland.

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, patch-clamp, cell viability assays.

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How to cite this article:
Kaproń B, Łuszczki J, Paneth A, Wujec M, Siwek A, Karcz T, Mordyl B, Głuch-Lutwin M, Gryboś A, Nowak G, Pająk K, Jóźwiak K, Tomczykowski A, Plech T. 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. Int J Med Sci 2017; 14(8):741-749. doi:10.7150/ijms.20001. Available from http://www.medsci.org/v14p0741.htm