Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The
acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation
of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has
again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most
prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common
approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam)
and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic
approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous
oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the
downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of
extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is
centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In
particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural
moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.
Keywords: AChE, BBB, chemical warfare agents, organophosphates, oxime, reactivator.
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