Sarin aging

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. 

Stojiljkovic, M.P., Pantelic, D., Maksimovic, M. (2001). Tabun, sarin, soman and VX poisoning in rats kinetics of inhibition of central and peripheral acetylcholinesterase, ageing, spontaneous and oxime-facilitated reactivation. Vll International Symposium on Protection against Chemical and Biological Agents. Stockholm, Sweden, June 15-19,... 

For example. Berry et al. (28) observed that, although pretreatment of animals with a combination of pralldoxlme (2 -FAH) and atropine Increased the LD50 values of several compounds (e.g., TEPP and DFP), It had little effect on the lethality of sarin and none on the lethality of soman they concluded that this was the result of the rapid aging of the ChEs inhibited by sarin and soman. More direct evidence of In vivo aging was obtained Harris et al. (29), who Injected P-labeled sarin and soman Into rats and observed that the rate of aging of the Inhibited rat-brain AChE was the same In vivo as in parallel In vitro experiments ... 

Cholinesterase.s that have been cxpo.sed to phosphorylat-ing agents (e.g.. sarin) become refractory to reactivation by cholinesterase reactivators. The process is called ttging and occurs both in vivo and in vitro with AChE and BuChE. Aging occurs by partial hydrolysis of the phosphorylated nioicty that is attached to the serine residue at the estcratic rite of the enzyme (Fig. 17-17). 

Chemistry The synthesis of soman is similar to that of sarin. The major alteration is that pinacolyl alcohol replaces isopropanol. Soman hydrolyzes over a range of pHs, with pinacolyl methylpho-sphonate and fluoride ions being the initial products. Subsequent hydrolysis of pinacolyl methyl-phosphonate is similar to the aging process associated with GD poisoning (below) (Michel et al., 1967). 

Based on multiple factors (total dose of atropine required aging half-times of the nerve agent 2 vs. 4 position of the oxime group (—C = N-OH) on the pyridine ring the number of oximes, both experimentally and commercially available, capable of reactivating cholinesterase and the percent of total cholinesterases that the oxime will reactivate) sarin (GB) and VX usually respond best to treatment. Tabun (GA) and cyclohexyl sarin (GF) are less responsive to treatment, and soman (GD) is the most difficult (least responsive) to treat. 

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