Prophylaxis by a reversible cholinesterase inhibitor and the NMDA receptor antagonist treatment as combinatorial countermeasure against nerve agent poisoning in mice model

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00605601" target="_blank" >RIV/68378041:_____/25:00605601 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/25:10492347 RIV/60162694:G44__/26:00564224
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S000927972500016X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S000927972500016X?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cbi.2025.111386" target="_blank" >10.1016/j.cbi.2025.111386</a>

Result language
angličtina
Original language name
Prophylaxis by a reversible cholinesterase inhibitor and the NMDA receptor antagonist treatment as combinatorial countermeasure against nerve agent poisoning in mice model
Original language description
The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed. The novel dually acting prophylactic drug (K1959) did not bring any additional benefit compared to the commonly used pyridostigmine. By contrast, an increase in the therapeutic efficacy of classic antidotal treatment was observed when the novel NMDA receptor antagonist (K2060) was combined with commonly used antidotes (oxime reactivator in combination with atropine). This novel combination reduced the acute toxicity of tabun, soman, and sarin more than two-fold, four-fold, and five-fold, respectively. These results highlight the possibility of NMDA antagonists such as K2060 as a supportive drug for the classic therapy of organophosphorus poisoning.
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
30104 - Pharmacology and pharmacy

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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