Antidotal treatment of GF-agent intoxication in mice with bispyridinium oximes
Language English Country Ireland Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
15590116
DOI
10.1016/j.tox.2004.07.019
PII: S0300-483X(04)00465-2
Knihovny.cz E-resources
- MeSH
- Antidotes chemistry therapeutic use toxicity MeSH
- Atropine therapeutic use MeSH
- Injections, Intramuscular MeSH
- Lethal Dose 50 MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Organophosphorus Compounds toxicity MeSH
- Organophosphate Poisoning * MeSH
- Poisoning drug therapy MeSH
- Oximes chemistry therapeutic use toxicity MeSH
- Pyridinium Compounds chemistry therapeutic use toxicity MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antidotes MeSH
- Atropine MeSH
- cyclohexyl methylphosphonofluoridate MeSH Browser
- Organophosphorus Compounds MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
It was shown that intoxications with GF-agent are rather resistant to convential oxime therapy; therefore, the development of new oximes in an effort to improve this unsatisfactory situation continues. Upon screening in vitro reactivation test for oximes, that were either newly synthesized at our department, or those that have never been tested for reactivation of GF-inhibited acetylcholinesterase (AChE), three oximes {(1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide) (K033); (1-(2-hydroxyiminomethylpyridinium)-3-(3-carbamoylpyridinium)-2-oxa-propane dichloride) (HS-6); and (1-(2-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)-but-2-ene dibromide) (BI-6)} with the highest reactivation potency were chosen for in vivo testing in our study. 1,3-Bis(4-hydroxyiminomethylpyridinium)-2-oxa-propane dibromide) (obidoxime); (1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride) (HI-6); and (1,1-bis(4-hydroxyiminomethylpyridinium)-methane dibromide) (methoxime) were chosen for comparison as a standard antidotal treatment. All the oximes were applied at the same proportion of their LD50 value (5%), and because of the different acute toxicity of the oximes, the molar concentrations of their solutions for intramuscular (i.m.) administration were considerably different. The highest therapeutic ratio was achieved for therapeutic regimen consisting of HI-6 and atropine. The significantly (P < 0.05) lowest effectivity in treatment of supralethal GF-agent poisoning in comparison with all the other therapeutic regimens, was surprisingly observed for methoxime. HS-6, K033 and BI-6 as well as obidoxime were comparably effective antidotes against GF-agent intoxication and their therapeutic ratios were similar.
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