Defense Against Chemical Warfare Agents and Toxic Industrial Chemicals (TICS).

摘要

Acetylcholinesterase (AChE) helps to regulate some of the most fundamental human biological operations such as motor function, sleep, attention, memory and emotions. A wide variety of AChE inhibitors exist, with health implications that range from fatal to benign. Strong AChE inhibitors such as some organophosphorus (OP) nerve agents (some of which can phosphorylate AChE irreversibly) are among the most powerful neurotoxins known and pose severe human health risks if misused. Weaker ligands, however, have been broadly studied as possible therapeutics for neural dysfunction disorders such as myasthenia gravis (MG), and various dementia such as Alzheimer's disease (AD). Weaker inhibitors have also been employed for nerve agent prophylaxis, although safety concerns continue to surround the standard prophylaxic formulations, especially pyridostiginine bromide (PB), suggesting that the criteria for their approval for military use might not be acceptable for broader civilian medical application. In fact, demonstrably safe and effective nerve agent prophylaxes remain elusive, despite a wealth of AChE inhibition data arising from AD and MG pharmaceutical research, as well as from pesticide toxicology studies.