Inhibition of blood cholinesterases following intoxication with VX and its derivatives

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 × LD50 (intramuscular administration), activities of cholinesterases in the blood were continuously monitored and half‐lives (t0.5) 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. Copyright © 2007 John Wiley & Sons, Ltd.