Toxicity, pharmacokinetics, and effectiveness of the ortho-chlorinated bispyridinium oxime, K870
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019292" target="_blank" >RIV/62690094:18470/22:50019292 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/23:00558178 RIV/00179906:_____/22:10447229
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0278691522004343?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0278691522004343?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.fct.2022.113236" target="_blank" >10.1016/j.fct.2022.113236</a>
Alternative languages
Result language
angličtina
Original language name
Toxicity, pharmacokinetics, and effectiveness of the ortho-chlorinated bispyridinium oxime, K870
Original language description
Oxime reactivators are causal antidotes for organophosphate intoxication. Herein, the toxicity, pharmacokinetics, and reactivation effectiveness of o-chlorinated bispyridinium oxime K870 are reported. Oxime K870 was found to have a safe profile at a dose of 30 mg/kg in rats. It exhibited rapid absorption and renal clearance similar to those of other charged oximes after intramuscular administration. Its isoxazole-pyridinium degradation product was identified in vivo. Although it showed some improvement in brain targeting, it was nevertheless rapidly effluxed from the central nervous system. Its reactivation effectiveness was evaluated in rats and mice intoxicated with sarin, tabun, VX, and paraoxon and compared with pralidoxime and asoxime. K870 was found to be less effective in reversing tabun poisoning compared to its parent unchlorinated oxime K203. However, K870 efficiently reactivated blood acetylcholinesterase for all tested organophosphates in rats. In addition, K870 significantly protected against intoxication by all tested organophosphates in mice. For these reasons, oxime K870 seems to have a broader reactivation spectrum against multiple organophosphates. It seems important to properly modulate the oximate forming properties (pK(a)) to obtain more versatile oxime reactivators.
Czech name
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Czech description
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Classification
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
Result continuities
Project
<a href="/en/project/GA21-03000S" target="_blank" >GA21-03000S: Modified nucleophiles for reactivation of cholinesterases inhibited by organophosphorus compounds</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Food and chemical toxicology
ISSN
0278-6915
e-ISSN
1873-6351
Volume of the periodical
167
Issue of the periodical within the volume
September
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
"Article Number: 113236"
UT code for WoS article
000828006900001
EID of the result in the Scopus database
2-s2.0-85133438055