title: Inhibition of blood cholinesterases following intoxication with VX and its derivatives.
abstract: Nerve agents can be divided into G-agents (sarin, soman, tabun, cyclosarin etc.) and V-agents. The studies dealing with V-agents (O-alkyl S-2-dialkylaminoethyl methyl phosphonothiolates) are limited to one or two representatives only (VX, Russian VX). Anticholinesterase properties of 11 V-agents were studied in rats in vivo. Following intoxication with these agents in doses of 1 x LD(50) (intramuscular administration), activities of cholinesterases in the blood were continuously monitored and half-lives (t(0.5)) of inhibition were determined. These values varied from 3 min (VX and some other agents) to 10-14 min (derivatives substituted on the phosphorus head by O-ethyl- or O-isopropyl-, and by dimethyl-, diethyl- and dibutyl- on the nitrogen). Acetylcholinesterase activities in selected parts of the brain and diaphragm (30 min after the intoxication) were also detected. A correlation between toxicities and rates of inhibition of the blood enzymes was demonstrated. A similar relationship between acetylcholinesterase inhibition in vitro (from literature data) and half-lives of the blood cholinesterases was also observed. Though the chemical similarity of V compounds is evident, marked differences were observed among different derivatives; however, all agents examined had high inhibition potency corresponding to their toxicities.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. bajgar@pmfhk.cz
authors.forename: J
authors.initials: J
authors.lastname: Bajgar
authors.forename: K
authors.initials: K
authors.lastname: Kuca
authors.forename: J
authors.initials: J
authors.lastname: Fusek
authors.forename: J
authors.initials: J
authors.lastname: Karasova
authors.forename: J
authors.initials: J
authors.lastname: Kassa
authors.forename: J
authors.initials: J
authors.lastname: Cabal
authors.forename: D
authors.initials: D
authors.lastname: Jun
authors.forename: V
authors.initials: V
authors.lastname: Blaha
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002802:Cholinesterases / Q000097:blood; D003964:Diaphragm / Q000201:enzymology; D005260:Female; D009946:Organothiophosphorus Compounds / Q000506:poisoning*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002800:Cholinesterase Inhibitors; D002802:Cholinesterases; D009946:Organothiophosphorus Compounds; C009680:VX-agent