Cholinesterase warfare agents

Cholinesterase inhibitor (anti-cholinesterase, ChEI) is a chemical that prevents cholinesterases (ChEs) from breaking down. ACh, which consequently increases the level and duration of action of this neurotransmitter. ChEIs such as organophosphates (esters of phosphoric acid) and carbamates (esters of carbamic acid) - serve as insecticides, pesticides, warfare agents and drugs. 

Dacre, J.C. 1984. Toxicology of some anticholinesterases used as chemical warfare agents - a review. In Cholinesterases Fundamental and Applied Aspects, M. Brzin, E.A. Barnard and D. Sket, eds., Walter de Gruyter, New York. pp. 415-426. 

Watson, A., Bakshi, K., Opresko, D., Young, R., Hauschild, V., King, J. (2006). Cholinesterase inhibitors as chemical warfare agents community preparedness guidelines. In Toxicology of Organophosphate and Carbamate Compounds (R.C. Gupta, ed.), pp. 47-68. Elsevier Academic Press, New York. 

SAFETY PROFILE A deadly human poison by skin contact and inhalation. (A small drop on the skin can kill a man.) A deadly experimental poison by ingestion, inhalation, skin contact, subcutaneous, intravenous, intramuscular, and intraperitoneal routes. Human systemic effects muscle weakness, bronchiolar constriction, nausea or vomiting, flaccid paralysis without anesthesia, miosis (pupOlar constriction), cholinesterase inhibition. A nerve gas used as a chemical warfare agent. To fight fire, use foam, CO2, drj chemical. When heated to decomposition or reacted with steam, it emits very toxic fumes of F and PO.. See also PARATHION. 

Irreversible inhibition occurs with organophos-phorus insecticides and chemical warfare agents (see p. 437) which combine covalently with the active site of acetylcholinesterase recovery of cholinesterase activity depends on the formation of new enzyme. Covalent binding of aspirin to cyclo-oxygenase... 

Chemical/Pharmacetical/Other Class Soman is a human-made nonpersistent anticholinesterase compound or organophosphate (OP) nerve agent, irreversible cholinesterase inhibitor, and chemical warfare agent. It is a light liquid with a camphorlike odor. 

Saxena, A. 2002, Human Serum Butyrylcholinesterase A Future Generation Antidote for Organophosphate Chemical Warfare Agent Toxicity, Proceedings of the Seventh International meeting on cholinesterases, Pucon, Chile. 

The incident described in the letter most likely was a result of applying in terrorist purposes of highly toxic substance (similar to chemical warfare agents inhibited cholinesterase), and by physicochemical properties similar to sarin. Exposure of people occurred by penetration of chemical substance via respiratory apparatus as no setting fine aerosol or vapour. Aerosol may be obtained using specially equipped tailpipe of a car as an aerosol generator. 

Currently, as discussed by the authors, the analytical methods mentioned above, with the exception of cholinesterase inhibition measurements and immunoassays, cannot yet be easily performed in field laboratories. For that reason, the immunochemical procedures for simple analysis of exposure to sulfur mustard described in this chapter may be a significant contribution to the early detection of exposure to this warfare agent. 

Many individuals have genetic susceptibility to certain chemicals (Calabrese 1978). The influence of these genetic differences likely produces sub- and supersensitivity to OP insecticides and warfare agents (Russell and Overstreet 1987). Several enzymes with variations or polymorphisms control sensitivity to OPs red blood cell acetylcholinesterase, serum cholinesterase or pseudocholinesterase, lymphocyte neuropathy target esterase or platelet neuropathy target esterase (NTE), serum paroxonase, butyrylcholinesterase, and serum arylesterase (Costa et al. 1999 LaDu 1988 Li et al. 1993 Mutch et al. 1992). Inhibition of red blood cell acetylcholinesterase, in both the central and the peripheral nervous systems, produces acute symptoms (Mutch et al. 1992). Paroxonase and arylesterase further modify the response (LaDu 1988 Li et al. 1993). Variant, inactive butyrylcho-linesterases increase sensitivity to OPs (Lockridge and Masson 2000 Schwarz et al. 1995). OP-induced delayed polyneuropathy results... 

One must appreciate that all cholinesterase inhibitors cannot be described easily under a single umbrella since it would include the widely used carbamates found in most household pesticides along with the deadly chemical warfare agents, which are some of the most potent chemicals ever developed by man. Although generalizations are sometimes useful, in the field of risk assessment they can be misleading and sometimes blatantly wrong. 

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