The Influence of Diazepam on the Antidotal Treatment-Induced Elimination of Acute Lethal Effects of Soman in Mice

Overview

Background.
The currently used antidotal treatment of intoxication with nerve agents, consisting of an anticholinergic drug and an acetylcholinesterase reactivator, is often completed with the anticonvulsive drug diazepam to prevent poisoned organisms from centrally mediated seizures and subsequent tonic-clonic convlusions. The aim of this study was to find out whether the complementation of the antidotal treatment with diazepam can influence antidotal treatment-induced elimination of acute lethal effects of the chosen nerve agent - soman.Methods and Results. In experiments on mice, the values of medium lethal dose of soman in the case of 24h surviving of soman-exposed mice, treated with the basic antidotes involving various types of anticholinergic drugs and acetylcholinesterase reactivators, were evaluated and compared tot he values of medium lethal dose of soman in mice treated with antidotes completed with diazepam. Our findings confirm that diazepam is able to enhance the efficacy of basic antidotal treatment to eliminate acute lethal effects of soman if atropin is used as anticholinergic drug. On the other hand, no ability of diazepam to enhance soman-induced lethal effects was demonstrated if an anticholinergic drug with central effects such as benactyzine, biperiden or scopolamin was used. The ability of diazepam to influence the efficacy of antidotes to eliminate soman-induced acute lethal effects was only observed in the case of using the oxime HI-6 as acetylcholinesterase reactivator.Conclusions. The most perspective antidotal mixture against soman, consisting of the oxime HI-6 and atropine, should be complemented by diazepam no only because of the prevention of poisoned organisms from centrally mediated seizures and subsequent tonic-clonic convulsions but also because of the increase in the ability of antidotal treatment to eliminate soman-induced acute lethal effects.

Key words:
soman, mouse, diazepam, HI-6, obidoxime, pralidoxime, atropine, benactyzine, biperiden, scopolamin