engleski

Medical chemical defence against chemical nerve agent threats

The high toxicity of organophosphorus compounds (OP ; tabun, sarin, VX, cyclosarin and soman) originates from the irreversible inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations call for immediate treatment, which usually consists of a combined administration of anticholinergic drugs and an aldoxime as the reactivator of AChE. Finding an optimal reactivator for prophylaxis against and post-treatment of OP toxicity is a continuing challenge. We identified several oximes with significantly improved human AChE reactivating efficacy against several OP and antidotal efficacy in mice when compared to standard reactivators. Further ex vivo testing of selected oximes and AChE mutants confirmed efficient oxime-assisted catalytic bioscavenging and neutralizing of OP exposure in whole blood. Therefore, our findings offer a platform for further antidote and scavenger development for nerve agents exposure. Supported by the Croatian Science Foundation (4307).

acetylcholinesterase, butyrylcholinesterase, organophosphorus compounds, reactivation

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