Abstract
The reactivating and therapeutic efficacy of two combinations ofoximes (HI-6 + trimedoxime and HI-6 + K203) was compared with the effectiveness of antidotal treatment involving single oxime (HI-6, trimedoxime, K203) using in vivo methods. In vivo determined percentage of reactivation of cyclosarin-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is slightly higher than the reactivating efficacy of the most effective individual oxime in blood, diaphragm as well as in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in cyclosarin-poisoned mice than the antidotal treatment involving single oxime. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings a beneficial effect for its ability to counteract the acute poisoning with cyclosarin.
Highlights
Classic nerve agents, such as tabun, sarin, soman, cy‐ closarin, and VX, are highly toxic organophosphorus compounds that present a serious threat to both military and civilian populations. They exert their biological effects by the inhibition of the enzyme acetylcholinesterase (AChE, EC 3.1.1.7) found at the receptor sites of tissue innervated by the cholinergic nervous system, which hydrolyzes the neuromediator acetycholine (ACh)
Trimedoxime, the oxime HI‐6 and the oxime K203 of 98% purity were synthesized at the Department of Toxicology of the Faculty of Mili‐ tary Health Sciences (Czech Republic)
It was able to increase the activity of cyclosarin‐inhibited AChE in blood by more than 90%, in diaphragm by more than 70% and in brain by more than 60%
Summary
Classic nerve agents, such as tabun, sarin, soman, cy‐ closarin, and VX, are highly toxic organophosphorus compounds that present a serious threat to both military and civilian populations. They exert their biological effects by the inhibition of the enzyme acetylcholinesterase (AChE, EC 3.1.1.7) found at the receptor sites of tissue innervated by the cholinergic nervous system, which hydrolyzes the neuromediator acetycholine (ACh). Some oximes (pralidoxime, obidoxime, trimedoxime, HI‐6) were developed and fielded to be used in the antidotal treat‐ ment of nerve agent poisonings, their reactivating efficacy is rather limited [5, 11]. While most of reactivators are sufficiently effective to reactivate sarin or VX‐inhibited
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