title: Distribution and elimination of the stereoisomers of soman and their effect on brain acetylcholine.
abstract: The four stereoisomers of soman (O-(1,2,2-trimethylpropyl)-methyl-fluorophosphonate) have been analyzed in vivo in mouse blood and tissues after administration of doses corresponding to 0.75 X LD50 of the two diastereoisomeric pairs of soman (Sc- and Rc-soman). The disappearance of the four isomers has been studied in vitro in the presence of enzymes involved in the toxicity and detoxification of soman, e.g., acetyl- and pseudocholinesterase, aliesterase, and phosphorylphosphatase. The effect of Sc- and Rc-soman on brain acetylcholine was studied in the mouse. The analytical methods used are based on gas chromatography-mass spectrometry with deuterated internal standards. Rc-Rp- and ScRp-soman, the two isomers that preferentially react with acetylcholinesterase, were found in blood and liver. In liver the concentration of ScRp was higher than that of RcRp and could be followed for 18 hr. In blood only ScRp could be found. Its presence there could be followed during 18 hr. The levels were, however, lower than in liver. The results indicate that the liver might be a depot for soman and that ScRp might be responsible for the delayed intoxication noted after treatment with antidotes. Rc-soman was found to have a more pronounced effect on the acetylcholine synthesizing system than has Sc-soman, which might explain its higher in vivo toxicity.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002091:Butyrylcholinesterase / Q000378:metabolism; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012999:Soman / Q000378:metabolism* / Q000633:toxicity; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D012999:Soman; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases; C045290:phosphorylphosphatase; D010744:Phosphoric Monoester Hydrolases; D002794:Choline; D000109:Acetylcholine