Nerve agents (
sarin,
soman,
cyclosarin,
tabun and
VX agent) and pesticides (
paraoxon,
chlorpyrifos,
TEPP) represent extremely toxic group of
organophosphorus compounds (OPCs). These compounds inhibit
enzyme acetylcholinesterase (AChE, EC 3.1.1.7) via its phosphorylation or phosphonylation at the
serine hydroxy group in its active site. Afterwards, AChE is not able to serve its physiological function and intoxicated organism is died due to overstimulation of
cholinergic nervous system. The current standard treatment of
poisoning with highly toxic OPCs usually consists of the combined administration of
anticholinergic drugs (preferably
atropine) and AChE reactivators (called "
oximes").
Anticholinergic drugs block effects of accumulated
neurotransmitter acetylcholine at nicotinic and
muscarinic receptor sites, while
oximes reactivate AChE inhibited by OPCs. Unfortunately, none from the currently used
oximes is sufficiently effective against all known
nerve agents and pesticides. Therefore, to find new
oximes able to sufficiently reactivate inhibited AChE (regardless of the type of OPCs) is still very important task for medicinal chemistry with the aim to improve the efficacy of antidotal treatment of the acute
poisonings mentioned. In this paper, the relationship between chemical structure of AChE reactivators and their ability to reactivate AChE inhibited by several
nerve agents and pesticides is summarized. It is shown that there are several structural fragments possibly involving in the structure of proposed AChE reactivators. Finally, an attempt of a future course of new AChE reactivators development is discussed.