Study of effects of novel PAM analogues on the treatment of poisoning by nerve agents

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A liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was validated and applied to the in vitro determination of novel PAM-type oximes, which can penetrate the blood-brain barrier(BBB) and reactivate acetylcholinesterase(AChE) inhibited by alkylphosphonate in various organs. It was indicated that the LC-MS/MS method could be a reliable method with high precision and accuracy for quantification of PAM-type oximes in various biological samples. On the other hand, although the oximes are potential antidotes to poisonings that inhibit AChE, but they are also toxic. To investigate the mechanism of their toxicity, the effects of oximes on the enzymes choline oxidase(ChOD) and cytochrome c oxidase(CyCOD) of the respiratory chain in mitochondria were examined. The results showed that the toxicities of oximes might be related to their inactivation of mitochondrial oxidase enzymes and generation of reactive oxygen species.