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 mg/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).

Department of Toxicology Faculty of Military Health Sciences University of Defence Hradec Králové

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Grant č. 0000501 MO0FVZ

Lit.: 34