Organophosphates (OPs) are useful agents as pesticides, but they also represent a serious threat when abused for terrorist attacks and chemical warfare. OP toxicity is due to the inhibition of acetylcholine esterase (AChE), the enzyme terminating the synaptic action of acetylcholine, resulting in a cholinergic crisis, which can be fatal due to respiratory failure and/or generalized seizures. Since standard therapy with atropine and established oxime-type enzyme reactivators (pralidoxime, obidoxime) is unsatisfactory, new bispyridinium (K-) oximes have been synthesized at the University of Hradec Kralove, Czech Republic, and are still continuously being developed. Over the last few years, we have been able to demonstrate that some of the K-oximes (K-27, K-48) have superior efficacy compared to pralidoxime and obidoxime. Even better, therapeutic results are obtained when oximes are administered before OP exposure. We have previously been able to show that the prophylactic efficacy of K-48 to protect from the toxic effects of the OP paraoxon exceeds that of the FDA-approved pretreatment compound pyridostigmine.
