In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD PHARMACOLOGY BRANCH
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Organophosphorus nerve agents irreversibly inhibit the enzyme acetylcholinesterase AChE, leading to excessive cholinergic neurotransmission and causing toxic lethal consequences. Current nerve agent therapies in the U.S. include 2-pralidoxime to reactivate inhibited AChE. Due to its quaternary structure, this oxime does not readily cross the blood brain barrier BBB to reactivate brain AChE and to mitigate CNS toxicity.
- Anatomy and Physiology