Evaluation of the Influence of Three Newly Developed Bispyridinium Anti‐nicotinic Compounds (MB408, MB442, MB444) on the Efficacy of Antidotal Treatment of Nerve Agent Poisoning in Mice

Evaluation of the Influence of Three Newly Developed Bispyridinium Anti‐nicotinic Compounds... The influence of three newly developed bispyridinium antinicotinic compounds (the non‐oximes MB408, MB442 and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with an oxime) of acute poisoning by the organophosphorus nerve agents tabun and soman was studied in mice. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non‐oximes was evaluated by determination of the LD50 values of the nerve agents and measurement of the survival time after supralethal poisoning. Addition of all the tested non‐oximes increased significantly the therapeutic efficacy of atropine in combination with an oxime against tabun poisoning. They also positively influenced the number of surviving mice 6 hr after supralethal poisoning with tabun. However, they were only slightly effective for the treatment of soman poisoning. The benefit of the tested bispyridinium non‐oximes was dose‐dependent. To conclude, the addition of bispyridinium non‐oximes to the standard antidotal treatment of acute poisoning with tabun was beneficial regardless of the chosen non‐oxime, but only slightly beneficial in the case of soman poisoning. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Basic and Clinical Pharmacology & Toxicology Wiley

Evaluation of the Influence of Three Newly Developed Bispyridinium Anti‐nicotinic Compounds (MB408, MB442, MB444) on the Efficacy of Antidotal Treatment of Nerve Agent Poisoning in Mice

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd
ISSN
1742-7835
eISSN
1742-7843
D.O.I.
10.1111/bcpt.12935
Publisher site
See Article on Publisher Site

Abstract

The influence of three newly developed bispyridinium antinicotinic compounds (the non‐oximes MB408, MB442 and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with an oxime) of acute poisoning by the organophosphorus nerve agents tabun and soman was studied in mice. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non‐oximes was evaluated by determination of the LD50 values of the nerve agents and measurement of the survival time after supralethal poisoning. Addition of all the tested non‐oximes increased significantly the therapeutic efficacy of atropine in combination with an oxime against tabun poisoning. They also positively influenced the number of surviving mice 6 hr after supralethal poisoning with tabun. However, they were only slightly effective for the treatment of soman poisoning. The benefit of the tested bispyridinium non‐oximes was dose‐dependent. To conclude, the addition of bispyridinium non‐oximes to the standard antidotal treatment of acute poisoning with tabun was beneficial regardless of the chosen non‐oxime, but only slightly beneficial in the case of soman poisoning.

Journal

Basic and Clinical Pharmacology & ToxicologyWiley

Published: Jan 1, 2018

References

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