Nerve, gases soman

The carbamate and OP insecticides and the organophosphorous nerve gases soman, sarin, and tabun all act as anticholinesterases, and most of their toxicity is attributed to this property. The naturally occurring carbamate physostigmine, which has been used in medicine, is also an anticholinesterase. Some OP compounds can cause relatively long-lasting inhibition of the enzyme because of the phenomenon of... 

Examples of organophosphates include the insecticides malathion, parathion, diazinon, fenthion, azinphos methyl, terbufos, dichlorvos, and chlorpyr-ifos the nerve gases soman, sarin, tabun, and VX the ophthalmic agent echothiophate the anthelmintic trichlorfon tricresyl phosphate-containing... 

However, severe constraints do exist on DoD use of IND drugs and vaccines for CBW defense in military combat. The issue of IND use arose in the Gulf War in the case of pyridostigmine bromide (PB), which was regarded as the most effective pretreatment against exposure to the nerve gas Soman, and pentavalent botulinum toxoid (BT)... 

Menger et al. synthesized a Ci4H29-attached copper(II) complex 3 that possessed a remarkable catalytic activity in the hydrolysis of diphenyl 4-nitrophenyl phosphate (DNP) and the nerve gas Soman (see Scheme 2) [21], When 3 was used in great excess (ca. 1.5 mM, which is more than the critical micelle concentration of 0.18 mM), the hydrolysis of DNP (0.04 mM) was more than 200 times faster than with an equivalent concentration of the nonmicellar homo-logue, the Cu2+-tetramethylethylenediamine complex 9, at 25°C and pH 6 (Scheme 4). The DNP half-life is calculated to be 17 sec with excess 1.5 mM 3 at 25°C and pH 6. The possible reasons for the rate acceleration with 3 were the enhanced electrophilicity of the micellized copper(II) ion or the acidity of the Cu2+-bound water and an intramolecular type of reaction due to the micellar formation. On the basis of the pH(6-8.3)-insensitive rates, Cu2+-OH species 3b (generated with pK3 < 6) was postulated to be an active catalytic species. In this study, the stability constants for 3 and 9 and the thermodynamic pvalue of the Cu2+-bound water for 3a —> 3b + H+ were not measured, probably because of complexity and/or instability of the metal compounds. Therefore, the question remains as to whether or not 3b is the only active species in the reaction solution. Despite the lack of a detailed reaction mechanism, 3 seems to be the best detoxifying reagent documented in the literature. 

Branching of the O-alkyl ester chain of organo-phosphorus compounds may introduce an asymmetric center, which together with an asymmetric substituted phosphorus atom creates a number of stereoisomers. Diastereoisomers may even be separated on a conventional capillary GC column. This is, for instance, the case with the nerve gas soman, which usually produces two peaks in a gas chromatogram. Although this is characteristic for identifying soman, it also increases the GC/MS detection limit by a factor of two. 

Klaidman, L.K., Adams, J.D., Jr., Cross, R., Pazdemik, T.L., Samson, F. (2003). Alterations in brain glutathione homeostasis induced by the nerve gas soman. Neurotox. Res. 5 177-82. Klegeris, A., McGeer, E.G., McGeer, P.L. (2007). Therapeutic approaches to inflammation in neurodegenerative disease. Curr. Opin. Neurol. 20 351-7. 

The FDA (2003) approved p3uidostigmine bromide for combat use by US military personnel to protect them from the lethal effects of the nerve gas soman (www.fda.gov/Drugs/EmergencyPreparedness/ BioterrorismandDrugPreparedness/ucml30342.hfm). 

Soman (GD) Pinoacolyl methylphosphonogluoridate fastest-killing nerve gas, produced in 1944 for the first time at I.G. Farben, Germany kills both through inhalation and skin contact. 

FDA approved PB as a pretreatment against Soman nerve gas in February 2003 (FDA, 2003a). 

A few of the estimated 50,000 organophosphates are shown in Figure 7-6. Many of the organophosphates (echothiophate is an exception) are highly lipid-soluble liquids. Echothiophate, a thiocholine derivative, is of clinical value because it retains the very long duration of action of other organophosphates but is more stable in aqueous solution. Soman is an extremely potent "nerve gas." Parathion and malathion are thiophosphate insecticides that are inactive as such they are converted to the phosphate derivatives in animals and plants and are used as insecticides. 

H.C. De Bisschop and E. Michiels, Assay of the nerve agent soman in serum by capillary gas chromatography with nitrogen-phosphorus detection and splitless injection, Chromatographia, 18, 433-436 (1984). 

Lallement, G. et al. Subchronic administration of various pretreatments of nerve gas poisoning n. Compared efficacy against soman toxicity. Drug Chem. Toxicol, 24, 165, 2001a. 

The three types of nerve agent known to have been weaponized are typified by sarin (GB), VX and tabun (GA). Soman (GD) and cyclosarin (GF) are less volatile phosphonofluo-ridate analogues of sarin, and RVX or R-33 is a Russian analogue of VX with broadly similar properties. Tabun differs from the other nerve agents in that it does not possess a P-methyl substituent, which has important implications for... 

Whereas there arc relatively few iV v/vo studies exploring a possible interaction of memantine with clinically available AChEIs, much more data have been published on the effects of memantine in animals treated with OP or carbamate (CM) insecticides used in agriculture or the household as well as in rodents experimentally intoxicated with the OP nerve ga.s. soman. 

Agriculture has been fortunate to be relatively free of mass outbreaks of OPIDN. The major chemical offender has been the plasticizer and lubricant trl-ortho-cresyl phosphate (TOCP). Contamination of various products with TOCP has paralyzed thousands of people since the turn of the century ( ). OPs in use In agriculture that have been shown to be neuropathic Include the cotton defoliant DEF and the pesticides EPN, haloxon and leptophos (not registered In the US). Neuropathic OPs used experimentally Include DFP and mlpafox one nerve gas (sarin) has been shown to cause OPIDN and there Is evidence another (soman) Is also a delayed neuropathic agent ( ). Recently, Wilson et al. ( ) found that isofenphos (IFF) caused OPIDN In hens. 

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