Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice – a comparison with oxime-based treatment

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F20%3A00556194" target="_blank" >RIV/60162694:G44__/20:00556194 - isvavai.cz</a>
Result on the web
<a href="https://www.tandfonline.com/doi/full/10.1080/15376516.2020.1817218" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/15376516.2020.1817218</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/15376516.2020.1817218" target="_blank" >10.1080/15376516.2020.1817218</a>

Result language
angličtina
Original language name
Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice – a comparison with oxime-based treatment
Original language description
Therapeutic efficacy of antidotal treatment of acute poisoning by nerve agents is generally assessed by the evaluation of LD50 values of nerve agents over 24 h following poisoning without or with a single administration of antidotal treatment. In this study, LD50 values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated poisoning were evaluated in mice for two experimental end points – 6 h and 24 h. While the efficacy of atropine or oxime-based antidotal treatment was the same regardless of the experimental end point, the therapeutic efficacy of all three newly developed bispyridinium non-oxime compounds (MB408, MB442, and MB444) was mostly slightly higher at the 6 h end point compared to the 24 h end point, although the therapeutic efficacy of MB compounds was not superior to oxime-based antidotal treatment. These results contrast with a study in guinea-pigs using a structurally-related compound, MB327, which showed a striking increase in protection at 6 h compared to 24 h. It is suggested that the disparity may be due to pharmacokinetic differences between the two animal species.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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