Comparison of reactivating and therapeutic efficacy of two salts of the oxime HI-6 against tabun, soman and cyclosarin in rats
Language English Country England, Great Britain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
17910616
DOI
10.1111/j.1742-7843.2007.00126.x
PII: PTO126
Knihovny.cz E-resources
- MeSH
- Muscarinic Antagonists pharmacology MeSH
- Atropine pharmacology MeSH
- Cholinesterase Inhibitors toxicity MeSH
- Rats MeSH
- Lethal Dose 50 MeSH
- Organophosphates antagonists & inhibitors toxicity MeSH
- Organophosphorus Compounds antagonists & inhibitors toxicity MeSH
- Oximes MeSH
- Pyridinium Compounds chemistry therapeutic use MeSH
- Cholinesterase Reactivators chemistry therapeutic use MeSH
- Soman antagonists & inhibitors toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Muscarinic Antagonists MeSH
- asoxime chloride MeSH Browser
- Atropine MeSH
- Cholinesterase Inhibitors MeSH
- cyclohexyl methylphosphonofluoridate MeSH Browser
- Organophosphates MeSH
- Organophosphorus Compounds MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- Soman MeSH
- tabun MeSH Browser
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.
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