BChE Reactivators for Nerve Agent and Pesticide OP Detoxification in Human Tissue

NIH CounterACT Exploratory/Developmental Projects in Translational Research (R21)


This project focused on the detoxification of nerve agent and pesticide organophosphates (OPs) directly in the tissue of OP-exposed individuals as a means of protecting them from both acute and chronic consequences of OP intoxication. It was based on two premises:

  • An oxime reactivator antidote, when combined with human butyrylcholinesterase (BChE), can degrade nerve agent and pesticide OP toxicants in vivo by converting BChE from a stoichiometric to a catalytic OP bioscavenger.
  • If adequate turnover is achieved through the administered oxime, the amounts of endogenous BChE naturally present in human tissue, primarily in plasma, lungs and intestines, should be sufficient to establish, in combination with an exogenously administered oxime, an efficient catalytic OP bioscavenger without supplemental administration of purified human BChE.