Inhibiting OP nerve agents

TABLE 66.1. Some AChE inhibiting OP nerve agents, pesticides, and prototype compounds... 

TABLE 72.1 Selected AChE Inhibiting OP Nerve Agents. Pesticides, and Prototype Compounds ... 

OPs are known to induce time-delayed neurotoxicity. This is due to the inhibition of an esterase in nerve tissue, neuropathy target esterase (NTE), that is also found in muscle and blood cells. The NTE level in the blood is an indicator of the inhibition of the enzyme. Inhibition of NTE and aging, the process of following the OP binding to an active esterase site that prevents the reactivation of the site, is important for selection of an antidote against certain OP nerve agents. It is of primary concern for Novichok agent. There is little information available on OP-caused neurotoxicity and the cardiac toxicity. 

The mechanism of AChE inhibition for aU the OP nerve agents is practically the same, i.e. phosphorylation or phosphonylation of the esteratic site of AChE. 

Both the toxicodynamics and toxicokinetics of OP nerve agents can be explained by their biochemical characteristics of interacting with cholinesterases and other hydrolases. Inhibition of cholinesterases in the blood is the first target for OPs according to the principle of first come, first served (Benschop and de Jong, 2001). 

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