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Comparison of Reactivating and Therapeutic Efficacy of Two Salts of the Oxime HI‐6 against Tabun, Soman and Cyclosarin in Rats
Author(s) -
Kassa Jiri,
Jun Daniel,
Kuca Kamil,
Bajgar Jiri
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2007.00126.x
Subject(s) - tabun , soman , nerve agent , chemistry , oxime , acetylcholinesterase , potency , pharmacology , sarin , biochemistry , medicine , enzyme , in vitro
The reactivating and therapeutic efficacy of two salts of the oxime HI‐6 (dichloride and dimethanesulphonate) against chosen nerve agents (tabun, soman and cyclosarin) was compared in rats. The potency of both salts of HI‐6 to decrease the acute toxicity of tabun, soman and cyclosarin was similar in nerve agent‐poisoned rats. While the potency of HI‐6 dichloride and HI‐6 dimethanesulphonate to counteract acute toxic effects of tabun is rather low, both salts of HI‐6 were able to decrease the acute toxicity of soman two times and acute toxicity of cyclosarin more than three times. The therapeutic efficacy of both salts of the oxime HI‐6 corresponds to their reactivating potency. While the reactivating efficacy of HI‐6 dichloride as well as HI‐6 dimethanesulphonate against tabun was negligible, their potency to reactivate soman‐inhibited acetylcholinesterase and cyclosarin‐inhibited acetylcholinesterase in peripheral (blood) and central (brain) compartment was relatively high. HI‐6 dichloride showed a somewhat higher potency to reactivate tabun‐inhibited acetylcholinesterase in brain, and soman‐inhibited acetylcholinesterase in blood and brain than HI‐6 dimethanesulphonate but the differences were not significant. Thus, the replacement of dichloride anion by dimethanesulphonate anion in the oxime HI‐6 does not influence the therapeutic and reactivating efficacy of the oxime HI‐6 against nerve agents. In addition, the higher solubility and stability of HI‐6 dimethanesulphonate in comparison with HI‐6 dichloride makes it possible to increase the dose and thus, the effectiveness of the oxime HI‐6 in the antidotal treatment of acute nerve agent poisonings.