Background:
Neurotoxic chemical warfare agents can be classified as some of the
most dangerous chemicals for humanity. The most effective of those agents are the
organophosphates (OPs) capable of restricting the enzyme acetylcholinesterase (AChE), which
in turn controls the nerve impulse transmission. When AChE is inhibited by OPs, its reactivation
can be usually performed through cationic oximes. However, until today it has not been
developed one universal defense agent, with complete effective reactivation activity for AChE
inhibited by any of the many types of existing neurotoxic OPs. For this reason, before treating
people intoxicated by an OP, it is necessary to determine the neurotoxic compound that was
used for contamination, in order to select the most effective oxime. Unfortunately, this task
usually requires a relative long time, raising the possibility of death. Cationic oximes also
display a limited capacity of permeating the blood-brain barrier (BBB). This fact compromises
their capacity of reactivating AChE inside the nervous system.
Methods:
We performed a comprehensive search on the data about OPs available on the
scientific literature today in order to cover all the main drawbacks still faced in the research for
the development of effective antidotes against those compounds.
Results:
Therefore, this review about neurotoxic OPs and the reactivation of AChE, provides
insights for the new agents’ development. The most expected defense agent is a molecule
without toxicity and effective to reactivate AChE inhibited by all neurotoxic OPs.
Conclusion:
To develop these new agents it is necessary the application of diverse scientific areas
of research, especially theoretical procedures as computational science (computer simulation,
docking and dynamics); organic synthesis; spectroscopic methodologies; biology, biochemical and
biophysical information; medicinal chemistry, pharmacology and toxicology.
