Title:Review about Structure and Evaluation of Reactivators of Acetylcholinesterase Inhibited with Neurotoxic Organophosphorus Compounds
Volume: 28
Issue: 7
关键词:
乙酰胆碱酯酶，活化剂，神经毒性有机磷化合物，肟，作战剂，化学防御作用。
摘要:
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 relatively 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 to 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, 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, is necessary.
