A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014332" target="_blank" >RIV/62690094:18470/18:50014332 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10373438 RIV/60162694:G44__/18:43889531

Výsledek na webu

<a href="https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-018-0196-3" target="_blank" >https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-018-0196-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40360-018-0196-3" target="_blank" >10.1186/s40360-018-0196-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase

Popis výsledku v původním jazyce

Background: Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods: To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results: Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k(r)) of 2142 min(-1). M-1, which was 51 times higher than that obtained for obidoxime (k(r) = 42 min(-1). M-1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion: According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.

Název v anglickém jazyce

A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase

Popis výsledku anglicky

Background: Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods: To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results: Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k(r)) of 2142 min(-1). M-1, which was 51 times higher than that obtained for obidoxime (k(r) = 42 min(-1). M-1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion: According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/GA15-16701S" target="_blank" >GA15-16701S: Koncept nekvarterních reaktivátorů AChE jakožto antidot otrav organofosfáty - nová naděje či slepá cesta?</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC pharmacology and toxicology

ISSN

2050-6511

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

21.2.2018

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

1-10

Kód UT WoS článku

000425777700001

EID výsledku v databázi Scopus

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