The effect of three newly developed bispyridinium non-
oxime compounds (
MB408,
MB442, and
MB444) on the therapeutic efficacy of a standard antidotal treatment (
atropine in combination with the
oxime HI-6 or
obidoxime) of acute
poisoning by two
nerve agents (
sarin and
cyclosarin) in mice was studied. 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 24 h LD50 values of the
nerve agents studied and by measurement of the survival time after supralethal
poisoning. Addition of all tested non-
oximes increased the therapeutic efficacy of
atropine in combination with an
oxime against
sarin poisoning; however, the differences were not significant. The non-
oximes also positively influenced the number of surviving mice 6 h after supralethal
poisoning with
sarin. In the case of
cyclosarin, they were also slightly beneficial in the treatment of acute
poisoning. The higher dose of
MB444 was able to significantly increase the therapeutic efficacy of standard antidotal treatment of
poisoning with
cyclosarin. The benefit of each bispyridinium non-
oxime compound itself was obviously dose-dependent. In summary, the addition of MB compounds to the standard antidotal treatment of acute
nerve agent poisoning was beneficial for the antidotal treatment of
sarin or
cyclosarin poisoning, although their benefit at 24 h after
poisoning was not significant, with the exception of the higher dose of
MB444 against
cyclosarin.