Jiŕi Bajgar 1, Victor Voicu 2, 3
1 Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2 Army Center for Medical Research, Bucharest, Romania
3 University of Medicine and Pharmacy “Carol Davila”, Faculty of Medicine, Department of Clinical Pharmacology, Toxicology and Psychopharmacology, Bucharest, Romania
Abstract
Background. Th e predominant types of poisonous gases included in the armies as chemical weapons are nerve agents like sarin, soman, and VX. As a basic trigger mechanism of the nerve agents action is described their infl uence on cholinergic nerve transmission caused by inhibition of acetylcholinesterase, butyrylcholinesterase and other hydrolases. Th e toxic eff ect of nerve agents will depend on the penetration rate of NA into the structures containing mentioned enzymes and on the rate and step of inhibition of functionally most important enzyme – acetylcholinesterase. Material and methods. Th e compounds studied were administered to female Wistar rats (Valez Praha) weighing 180 – 220 g by diff erent routes of administration (i.v., i.m., i.p., p.o., s.c. and p.c.). The monitoring of blood acetylcholinesterase activity and normal activity (serving as a individual control value for each animal) was registered. Following intoxication, registered decrease of acetylcholinesterase activity was evaluated in semilogarithmical transformation and the half-times (t0.5) of inhibition in vivo were calculated. For every compound and route of administration, 4-8 animals were used. Results. Th e decrease of acetylcholinesterase activity is very fast, practically without delay after the injection of EDMM [O-ethyl-S-(2-dimethylaminoethyl)- methylphosphothioate]; following s.c. administration, the rate of acetylcholinesterase activity decrease was not so high as that observed for i.m. administration and this decrease was slower following p.o. and p.c. administration, respectively. Conclusions. Comparison of the “eff ective” doses shows that this dose is lowest one for VX followed by EDMM, sarin and soman. From this point of view, VX is the most eff ective compound from the nerve agents studied and therefore its including in the military arsenals is also comprehensible taking into account its mechanism of action.