Soman aging

Another disadvantage of the first generation reactivators lies in their lacking of antidotic effect in respect to affections induced by soman, which causes fast aging of the phosphorylated enzyme. 

A positive property of the most active reactivators of the second generation lies in their ability to reduce 2 to 2.5 times aging rate of AChE inhibited with soman. 

In dogs poisoned with soman (Intravenously at 30 pg/kg) and treated with I at 104 mg/kg (Intravenously 31/2 min after soman), the large dose of I stopped aging of Inhibited cholinesterase and reactivated 24.0% and 35.6% of the red-cell and diaphragm cholinesterase activities, respectively. It failed to reactivate brain cholinesterase. Indeed, the brain acetylcholinesterase activity after the treatment with 1 was lower than that just before the injection of I. The last finding indicates the inability of I to cross the blood-brain barrier in significant quantities. 

Soman Blood Adduct to BuChE Not found in human exposures because of rapid aging GC-NPD, FPD, MS Van der Schans et al (2004a)... 

A major drawback of the fluoride reactivation method is that not all nerve agent adducts are amenable to fluoride reactivation, with the aged adduct of soman the best known example. This problem can be solved by looking at the BuChE enzyme itself Fidder et al (2002) published a method based on the LC-MS analysis of a nerve agent phosphylated nonapeptide derived after pepsin digestion of inhibited butyrylcholinesterase. The authors presented a procedure to extract BuChE from plasma using... 

These examples show that OPs can bind covalently to albumin under physiological conditions, and that the resultant adducts are relatively stable. OP-albumin adducts could therefore be useful as biomarkers of OP exposure. In addition, unlike cholinesterases, the soman-albumin conjugate does not age (Li et al, 2008a), making it possible to discriminate between sarin and soman exposure. OP-albumin adducts have not yet been reported in humans exposed to OPs. 

Standard post-exposure treatments include eoneurrent administration of anticholinergics, such as the musearinie cholinergic blocker atropine sulfate, and AChE reactivators, such as obidoxime and pyridine-2-aldoxime methochloride (also known as 2-PAM). Oximes cannot reactivate OP-inhibited AChE that has already aged . Therefore, traditional oxime treatment is considered to be less effective for those agents such as soman, for which aging is rapid (Worek et al, 2005). 

Talbot, B.G., Anderson, D.R., Harris, L.W., Yarbrough, L.W., Lermox, W.J. (1988). A comparison of in vivo and in vitro rates of aging of soman-inhibited erythrocyte AChE in different animal species. Drug Chem. Toxicol. 11(3) 289-305. 

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