Organophosphorus-based (OP) nerve agents represent the most toxic class of chemical warfare (CW) agents. Despite efforts to control threats (the Organization for Prohibition of Chemical Weapons, OPCW), the use of CWs continues to remain a major concern for both military and civilian populations. To counteract the rapid toxicity upon exposure, currently fielded therapies include an acetylcholinesterase (AChE) oxime reactivator, pralidoxime chloride (2-PAM), to reactive inhibited AChE and a competitive muscarinic receptor antagonist, atropine, to mitigate excitotoxicity from excess acetylcholine. While 2-PAM has demonstrated some efficacy, efforts to develop a replacement AChE oxime reactivator with enhanced antidotal efficacy have been ongoing. Using an iterative approach that combines synthetic chemistry, computation, and in vitro and in vivo evaluation, we have recently developed a new candidate oxime (LLNL-02) that exhibits blood-brain barrier penetration and significant reactivation capacity. Here, we will present efficacy outcomes against sarin in the guinea pig. Survival, blood and brain AChE will be presented relative to 2-PAM.<br/>

Evaluating the efficacy of a novel oxime reactivator against nerve agent exposure

2019 Fall National Meeting

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