Evaluation of Potency of Known Oximes (Pralidoxime, Trimedoxime, HI-6, Methoxime, Obidoxime) to in vitro Reactivate Acetylcholinesterase Inhibited by Pesticides (Chlorpyrifos and Methylchlorpyrifos and Nerve Agent (Russian VX)

Kamil Musílek,Kamil Kuča,Daniel Jun

doi:10.14712/18059694.2017.83

Kamil Musílek, Kamil Kuča + Show 1 more

Open Access

https://doi.org/10.14712/18059694.2017.83

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Abstract

Nerve agents and pesticides belong to the group of organophosphates. They are able to inhibit irreversibly the enzyme acetylcholinesterase (AChE). Acetylcholinesterase reactivators were designed for the treatment of nerve agent intoxications. Their potency to reactivate pesticide-inhibited AChE was many times evaluated. In this study, five commonly used AChE reactivators (pralidoxime, methoxime, HI-6, obidoxime, trimedoxime) for the reactivation of AChE inhibited by two pesticides (chlorpyrifos and methylchlorpyrifos) were used. Russian VX (nerve agent) as a member of nerve agents' family was taken for comparison. Obtained results show that oximes developed against nerve agent intoxication are less effective for intoxication with organophosphorus pesticides. Especially, methylchlorpyrifos-inhibited AChE was found to be poorly reactivated by the compounds used.

Highlights

Organophosphate compounds (OPC) are well known as substances developed in the past for military purposes
Their reactivation activity was tested in vitro on OPC-inhibited AChE using a modification of standard reactivation test [8]
The relationship between concentration and reactivation efficacies of studied reactivators is shown in Fig. 3 and Fig. 4

Summary

Introduction

Organophosphate compounds (OPC) are well known as substances developed in the past for military purposes (nerve agents – e.g. tabun – GA, Russian VX – RVX or VX) At present, they are widely spread as pesticides in agriculture (e.g. chlorpyrifos – CPF, methylchlorpyrifos – MCPF, parathion – PTH) as potential therapeutics in medicine or used for various purposes in the industry (Fig. 1) [1,12]. They are widely spread as pesticides in agriculture (e.g. chlorpyrifos – CPF, methylchlorpyrifos – MCPF, parathion – PTH) as potential therapeutics in medicine or used for various purposes in the industry (Fig. 1) [1,12] These compounds inhibit irreversibly the enzyme acetylcholinesterase (AChE, EC 3.1.1.7). The depression of breathing centre occur and cause the death by ventilation failure [1]

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