Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice – a comparison with oxime-based treatment. (21st November 2020)

• Record Type: Journal Article
• Authors: Kassa, Jiri; Timperley, Christopher M.; Bird, Mike; Green, A. Christopher; Tattersall, John E. H.
• Is Part Of: Toxicology mechanisms and methods. Volume 30:Number 9(2020)
• Page Start: 703
• Page End: 710
• Publication Date: 2020-11-21
• Subjects: Nerve agents -- atropine -- MB compounds -- oximes -- mice; Analytical toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology -- Methodology -- Periodicals; 615.907
• DOI: 10.1080/15376516.2020.1817218
• Languages: English
• ISSNs: 1537-6516

Abstract

Abstract: Therapeutic efficacy of antidotal treatment of acute poisoning by nerve agents is generally assessed by the evaluation of LD50 values of nerve agents over 24 h following poisoning without or with a single administration of antidotal treatment. In this study, LD50 values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated poisoning were evaluated in mice for two experimental end points − 6 h and 24 h. While the efficacy of atropine or oxime-based antidotal treatment was the same regardless of the experimental end point, the therapeutic efficacy of all three newly developed bispyridinium non-oxime compounds (MB408, MB442, and MB444) was mostly slightly higher at the 6 h end point compared to the 24 h end point, although the therapeutic efficacy of MB compounds was not superior to oxime-based antidotal treatment. These results contrast with a study in guinea-pigs using a structurally-related compound, MB327, which showed a striking increase in protection at 6 h compared to 24 h. It is suggested that the disparity may be due to pharmacokinetic differences between the two animal species.