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The present approaches to the development of prophylactic and therapeutic antidotes against nerve agents Nerve agents belong to highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. Basic mechanism of action of nerve agents is based on acetylcholinesterase (AChE, EC 3.1.1.7) inhibition and subsequent accumulation of neuromediator acetylcholine at the cholinergic synapses, either peripheral or central leading to cholinergic hyperstimulation and development of symptoms of poisoning, followed by metabolic dysbalance and death without effective prophylaxis/treatment. The antidotal treatment of acute poisonings with nerve agents still represents a serious problem and, therefore, we are searching how to satisfactorily protect people against acute toxicity of nerve agents. There are two approaches how to improve the medical protection against nerve agents: to increase the resistance of nerve agent-exposed organism and the efficacy of post-exposure antidotal treatment by pharmacological prophylaxis the development of new, more effective antidotes, expecially AChE reactivators, to achieve the satisfactorily effective antidotal treatment of acute poisonings with nerve agents.