Abstract : The research completed within this contract focused on the development of a platform that reverses the effects of an analgesic overdose (Tasks 1-3), and the development a platform that reverses the effects associated with organophosphate poisoning (Task 4). We successfully scaled up the synthesis of the naloxone prodrug that was designed and tested during Phases I and II, and documented its efficacy in a pig model. Although we had proposed to develop a long-acting form of ketamine, regulatory issues prevented us from moving that project forward. Finally, we designed a novel class of dendrimer-oxime drug conjugates, and evaluated the mechanism by which these conjugates hydrolyze paraoxon.