Nerve agents mechanisms

Toxins present a variety of both incapacitating and lethal effect. Most toxins of military significance can be broadly classified in one of two ways. Neurotoxins disrupt the nervous system and interfere with nerve impulse transmission similar to nerve agents (Chapter 1). However, all neurotoxins do not operate through the same mechanism of action or do they produce the same symptoms. Cytotoxins are poisons that destroy cells or impair cellular activities. Symptoms may resemble those of vesicants (Chapter 3) or they may resemble food poisoning or other diseases. Toxins may also produce effects that are a combination of these general categories. The consequences of intoxication from any individual toxin can vary widely with route of exposure and dose. In addition, some toxins act as biomediators and cause the body to release excessive, and therefore harmful, amounts of chemicals that are normally produced by the body. 

Bajgar J (2004) Organophosphates/nerve agent poisoning mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 38 151-216... 

Vesicants, nerve agents, and phosgene are reactive electrophiles that react covalently with nucleophilic sites on macro molecules. Reactive nucleophilic sites exist on the bases and phosphate groups of DNA molecules. An advantage of DNA as a substrate is that it is present in all tissues of the body. A disadvantage is that repair mechanisms tend to excise the alkylated moiety, resulting in a much shorter lifetime compared to alkylated proteins (for a recent review of mass spectrometry for quantitation of DNA adducts, see Koc and Swen-berg <2>). 

GD is likely to undergo hydrolysis in most soils. As noted above, the rate of hydrolysis will be dependent upon temperature and pH. According to Morrill et al. (1985), evaporation is the primary mechanism for the loss of the GA and GB nerve agents from soil. Although the G agents are liquids under ordinary environmental conditions, their relatively high volatility and vapor pressure permits them to be disseminated in vapor form. Because of this volatility, GD is not expected to persist in soils. 

McDonough, J.H., Shih, T-M. (1997). Neuropharmacological mechanisms of nerve agent-induced seizure and neropathol-ogy. Neurosci. Behav. Rev. 21 559-79. 

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