In-Vitro Searching for a New Potent Reactivator of Acetylcholinesterase Inhibited by Nerve Agent VX

Abstract

Abstract: Organophosphorus compounds, especially nerve agents, inhibit enzyme acetylcholinesterase(AChE; EC 3.1.1.7) in an irreversible manner. Atropine plus an oxime reactivator are used as an effectivetreatment of organophosphate poisoning. In this work, we have evaluated reactivation potency of twentyreactivators of different chemical structures in reactivation of VX-inhibited AChE. Rat brain AChE homogenatewas used as the appropriate source of the enzyme. According to our results, trimedoxime seems to be the mostpotent reactivator of VX-inhibited AChE at the concentration 10 -3 M. Keywords: Nerve agent, reactivation, inhibition, acetylcholinesterase, trimedoxime, oxime, VX agent. INTRODUCTION organophosphate poisoning. Oxime reactivators break thebond between enzyme and organophosphate and restore thefunctional enzyme (Scheme 1 – Reactivation). However,none from the currently used AChE reactivators is able tosatisfactorily reactivate AChE inhibited by all kinds of OPs[2a].Organophosphorus compounds (OPs) have been widelyused as pesticides in many parts of the world and have beenalso misused as chemical warfare agents [1]. From thisgroup, nerve agents are the most known [2]. In the past, theywere also used in terroristic attack in Tokyo subway [3].Therefore, the threat of the intoxication with OPs isrelatively high. The most potent nerve agents are representedMany laboratories over the world are interested in thesynthesis of the so-called “broad spectrum” reactivator that