The therapeutic efficacy of treatments for acute intoxication with highly toxic
organophosphorus compounds, called
nerve agents, usually involves determination of LD50 values 24 h after
nerve agent challenge without and with a single administration of the treatment. Herein, the LD50 values of four
nerve agents (
sarin,
soman,
tabun and
cyclosarin) for non-treated and treated intoxication were investigated in mice for experimental end points of 6 and 24 h. The LD50 values of the
nerve agents were evaluated by probit-logarithmical analysis of deaths within 6 and 24 h of i.m. challenge of the
nerve agent at five different doses, using six mice per dose. The efficiency of
atropine alone or
atropine in combination with an
oxime was practically the same at 6 and 24 h. The therapeutic efficacy of the higher dose of the antinicotinic compound
MB327 was slightly higher at the 6 h end point compared to the 24 h end point for
soman and
tabun intoxication. A higher dose of
MB327 increased the therapeutic efficacy of
atropine alone for
sarin,
soman and
tabun intoxication, and that of the standard antidotal treatment (
atropine and
oxime) for
sarin and
tabun intoxication. The therapeutic efficacy of
MB327 was lower than the
oxime-based antidotal treatment. To compare the 6 and 24 h end points, the influence of the experimental end point was not observed, with the exception of the higher dose of
MB327. In addition, only a negligible beneficial impact of the compound
MB327 was observed. Nevertheless, antinicotinics may offer an additional avenue for countering
poisoning by
nerve agents that are difficult to treat, and synthetic and biological studies towards the development of such novel drugs based on the core bispyridinium structure or other molecular scaffolds should continue.