SUMMARY
Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) is one of the highly toxic organophosphorus
compounds misused as chemical warfare agents for military as well as terroristic purposes. It differs from
other highly toxic organophosphates in its chemical structure and by the fact that the commonly used
antidotes (atropine in combination with an oxime) are not able to sufficiently eliminate its acute toxic
effects.
The neuroprotective effects of the newly developed oximes (K027, K048) or trimedoxime in
combination with atropine (atropine, K027/atropine, K048/atropine and trimedoxime/atropine mixtures)
on rats poisoned with tabun at a lethal dose (270 micro g/kg i.m.; 120% of LD50 value) were studied. The
tabun-induced neurotoxicity was monitored using a functional observational battery and an
automaticmeasurement of motor activity. The neurotoxicity of tabun was monitored at 24 hours and
7 days following tabun challenge. The results indicate that atropine alone is not able to protect rats from
the lethal effects of tabun. Five non-treated tabun-poisoned rats and five tabun-poisoned rat treated with
atropine alone died within 24 hours. On the other hand, atropine combined with all tested oximes allows
most tabun-poisoned rats to survive within 7 days following tabun challenge. All three oximes tested
combined with atropine seem to be sufficiently effective antidotes for a decrease in tabun-induced
neurotoxicity in the case of lethal poisonings, although they are not able to eliminate tabun-induced
neurotoxicity completely. Due to their neuroprotective effects, all the tested oximes appear to be more
suitable oximes for the antidotal treatment of acute tabun exposure than the currently used oximes
(pralidoxime, obidoxime, HI-6).
KEY WORDS
neuroprotective; neurotoxicity; oxime; rat; tabun
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