Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875618" target="_blank" >RIV/60162694:G44__/16:43875618 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.tandfonline.com/doi/full/10.3109/15376516.2016.1162249" target="_blank" >http://www.tandfonline.com/doi/full/10.3109/15376516.2016.1162249</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3109/15376516.2016.1162249" target="_blank" >10.3109/15376516.2016.1162249</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice

Popis výsledku v původním jazyce

The potency of the bispyridinium non-oxime compound MB327 [1,1-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide] to increase the therapeutic efficacy of the standard antidotal treatment (atropine in combination with an oxime) of acute poisoning with organophosphorus nerve agents was studied in vivo. The therapeutic efficacy of atropine alone - or atropine in combination with an oxime, MB327, or both an oxime and MB237 - was evaluated by the determination of LD50 values of several nerve agents (tabun, sarin and soman) in mice with and without treatment. The addition of MB327 increased the therapeutic efficacy of atropine alone, and atropine in combination with an oxime, against all three nerve agents, although differences in the LD50 values only reached statistical significance for sarin. In conclusion, the addition of the compound MB327 to the standard antidotal treatment of acute poisonings with nerve agents was beneficial regardless of the chemical structure of the nerve agent, although at the dose employed, MB327 in combination with atropine, or atropine and an oxime, provided only a modest increase in protection ratio. These results from mice, and previous ones from guinea-pigs, provide consistent evidence for additional, albeit modest, efficacy resulting from the inclusion of the antinicotinic compound MB327 in standard antidotal therapy. Given the typically steep probit slope for the dose-lethality relationship for nerve agents, such modest increases in protection ratio could provide significant survival benefit.

Název v anglickém jazyce

Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice

Popis výsledku anglicky

The potency of the bispyridinium non-oxime compound MB327 [1,1-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide] to increase the therapeutic efficacy of the standard antidotal treatment (atropine in combination with an oxime) of acute poisoning with organophosphorus nerve agents was studied in vivo. The therapeutic efficacy of atropine alone - or atropine in combination with an oxime, MB327, or both an oxime and MB237 - was evaluated by the determination of LD50 values of several nerve agents (tabun, sarin and soman) in mice with and without treatment. The addition of MB327 increased the therapeutic efficacy of atropine alone, and atropine in combination with an oxime, against all three nerve agents, although differences in the LD50 values only reached statistical significance for sarin. In conclusion, the addition of the compound MB327 to the standard antidotal treatment of acute poisonings with nerve agents was beneficial regardless of the chemical structure of the nerve agent, although at the dose employed, MB327 in combination with atropine, or atropine and an oxime, provided only a modest increase in protection ratio. These results from mice, and previous ones from guinea-pigs, provide consistent evidence for additional, albeit modest, efficacy resulting from the inclusion of the antinicotinic compound MB327 in standard antidotal therapy. Given the typically steep probit slope for the dose-lethality relationship for nerve agents, such modest increases in protection ratio could provide significant survival benefit.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FP - Ostatní lékařské obory

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Toxicology Mechanisms and Methods

ISSN

1537-6516

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

334-339

Kód UT WoS článku

000380053100004

EID výsledku v databázi Scopus

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