The potency of newly developed monoxime bispyridinium compounds (K156, K203) in reactivating
tabun-inhibited
acetylcholinesterase and reducing
tabun-induced lethal toxic effects was compared with commonly used
oximes (
obidoxime,
trimedoxime, the
oxime HI-6) using in vivo methods. Studies determining percentage of reactivation of
tabun-inhibited blood and tissue
acetylcholinesterase in poisoned rats showed that the reactivating efficacy of newly developed
oxime K203 is comparable with
obidoxime and
trimedoxime in blood and higher than the reactivating potency of
trimedoxime and
obidoxime in diaphragm and brain, where the difference in reactivating efficacy of
obidoxime,
trimedoxime and K203 is significant. On the other hand, the potency of newly developed K156 to reactivate
tabun-inhibited
acetylcholinesterase is comparable with
obidoxime or
trimedoxime in diaphragm and brain. It is significantly lower than the reactivating efficacy of
trimedoxime and
obidoxime in blood. Moreover, both newly developed
oximes were found to be relatively efficacious in the reduction of lethal toxic effects in
tabun-poisoned mice. Especially, the
oxime K203 is able to decrease the acute toxicity of
tabun nearly two times. The therapeutic efficacy of K156 and K203 corresponds to their potency to reactivate
tabun-inhibited
acetylcholinesterase, especially in diaphragm and brain. In contrast to
obidoxime and
trimedoxime, the
oxime HI-6 is not effective in reactivation of
tabun-inhibited acetycholinesterase and in reducing
tabun lethality. While the
oxime K156 does not improve the reactivating and therapeutic effectiveness of currently available
obidoxime and
trimedoxime, the newly developed
oxime K203 is markedly more effective in reactivation of
tabun-inhibited
acetylcholinesterase in rats, especially in brain, and in reducing lethal toxic effects of
tabun in mice and, therefore, it is suitable for the replacement of commonly used
oximes for the antidotal treatment of acute
tabun poisoning.