Two Possibilities How to Increase the Efficacy of Antidotal Treatment of Nerve agent Poisonings

J.      Kassa; K.      Musilek; J.      Zdarova Karasova; K.      Kuca; J.      Bajgar

doi:10.2174/138955712798869011

Abstract

Highly toxic organophosphorus inhibitors of acetylcholinesterase referred as nerve agents are considered to be among the most dangerous chemical warfare agents. The oximes represent very important part of medical countermeasures of nerve agent poisonings. They are used to reactivate the nerve agent-inhibited acetylcholinesterase. Despite long-term research activities, there is no single, broad-spectrum oxime suitable for the antidotal treatment of poisoning with all organophosphorus agents. There are two approaches how to increase and broaden the effectiveness of antidotal treatment of poisoning with nerve agents - to develop new structural analogues of currently available oximes and/or to combine currently available or newly developed oximes. The review describes the evaluation of the potency of newly developed oximes (especially the oxime K203) or combinations of oximes to reactivate nerve agent-inhibited acetylcholinesterase and to counteract the acute toxicity of nerve agents in comparison with single commonly used oxime (obidoxime, trimedoxime or HI-6).

Keywords: Acetylcholinesterase, antidotal treatment, combination of oximes, nerve agents, fluorophosphonates, cyclosarin, organophosphorus insecticides, trimedoxime, oximes, monopyridinium, non-phosphonylated, hydroxyiminomethyl