Effect of Diazepam on Antidotal Therapy of Lethal Toxic Effects of Soman in the Rat

Overview

Experiments on male rats examined the effect of a basic antidotal therapy consisting of various types of anticholinergic substances and reactivators of acetylcholinesterase on the lethal effects of the highly toxic organophosphorous compound soman by means of determination of the medium lethal dose of soman in 24-bour survival of experimental animals. The efficacy of the basic antidotal therapy of acute intoxications by soman evaluated in this way was compared with the effect of an antidotal therapy enriched with diazepam, a drog with anticonvulsive action. The obtained results show tkat addition of diazepam to the basic antidotal therapy increases the ability of the antidotal therapy to eliminate acute lethal effects of soman if it includes atropine as an anticholinergic agent regardless of the employed type of acetylcholinesterase reactivator. In the tase of employment of anticholinergic agents with prevailing central effects, such as benactyzine, biperiden, or scopolamine, the addition of diazepam will not significantly influence the therapeutic efficacy of the antidotal therapy regardless of the selected aetylcholinesterase reactivator. At the same time, the addition of diazepam to the antidotal therapy does not change the difference in the efficacy of the antidotal therapy in dependence on the selected anticholinergic agent or acetylcholinesterase reactivator. At present the most common combination of antidotns against soman, consisting of obidoxime and atropine, as well as a prospective combination containing oxime HI-6 and atropine should be supplemented with diazepam not only to prevent centrally induced seizures and tonic-clonit convulsions bot also to increase the ability of such antidotal therapy to eliminate acute lethal toxicity of soman.

Key words:
soman - rat - diazepam - HI-6 - obidoxime - pralidoxime - atropine - benactyzine - biperiden - scopolamine