Evaluation of the Influence of Three Newly Developed Bispyridinium Anti-nicotinic Compounds (MB408, MB442, MB444) on the Efficacy of Antidotal Treatment of Nerve Agent Poisoning in Mice
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
29117635
DOI
10.1111/bcpt.12935
Knihovny.cz E-resources
- MeSH
- Antidotes chemical synthesis pharmacology therapeutic use MeSH
- Atropine pharmacology MeSH
- Drug Therapy, Combination MeSH
- Lethal Dose 50 MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Nerve Agents poisoning MeSH
- Nicotinic Agonists chemical synthesis pharmacology MeSH
- Organophosphates toxicity MeSH
- Organophosphate Poisoning drug therapy etiology MeSH
- Oximes pharmacology MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridinium Compounds chemical synthesis pharmacology therapeutic use MeSH
- Soman poisoning MeSH
- Drug Synergism MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antidotes MeSH
- Atropine MeSH
- MB408 MeSH Browser
- MB442 MeSH Browser
- MB444 MeSH Browser
- Nerve Agents MeSH
- Nicotinic Agonists MeSH
- Organophosphates MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Soman MeSH
- tabun MeSH Browser
The influence of three newly developed bispyridinium antinicotinic compounds (the non-oximes MB408, MB442 and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with an oxime) of acute poisoning by the organophosphorus nerve agents tabun and soman was studied in mice. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non-oximes was evaluated by determination of the LD50 values of the nerve agents and measurement of the survival time after supralethal poisoning. Addition of all the tested non-oximes increased significantly the therapeutic efficacy of atropine in combination with an oxime against tabun poisoning. They also positively influenced the number of surviving mice 6 hr after supralethal poisoning with tabun. However, they were only slightly effective for the treatment of soman poisoning. The benefit of the tested bispyridinium non-oximes was dose-dependent. To conclude, the addition of bispyridinium non-oximes to the standard antidotal treatment of acute poisoning with tabun was beneficial regardless of the chosen non-oxime, but only slightly beneficial in the case of soman poisoning.
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