The effects of pretreatment with soman simulator in the skeletal muscle: direct interactions with acetylcholinesterase.
Soman simulator PDP is a compound that has a chemical structure identical to soman, except that the fluorine atom is replaced by a methyl group which makes PDP unable to bind covalently to the AChE active center. In rats, late mortality observed after treatment with high doses of soman could be prevented by PDP pretreatment. Such pretreatment has been much less efficient in primates. The effect of PDP in rats has been explained by blocking the deposition of soman in so-called soman depots in which soman is stored intact and subsequently released. In this paper we demonstrate that in the presence of PDP, inhibition of rat muscle AChE by soman is reduced in rat but not in human muscle homogenates. This result suggests that at least part of the beneficial effects of PDP pretreatment in rat might be due to the direct interaction of PDP with AChE resulting in reduced AChE phosphorylation by soman.
Grubic
Z
Z
Institute of Pathophysiology, School of Medicine, University of Ljubljana, Slovenia.
Brank
M
M
Brzin
M
M
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007700:Kinetics; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
D002800:Cholinesterase Inhibitors; C048957:pinacolyl dimethylphosphinate; D012999:Soman; D000110:Acetylcholinesterase