engleski

Antidotal efficacy of new quinuclidinium and imidazolium oximes combined with HI-6 or diazepam in tabun and soman intoxication

Conventional medical treatment against the intoxication with organophosphorus (OP) compounds consists of anticholinegic drugs to counteract the accumulation of acethylcholine and oxime to reactivate OP-inhibited acethylcholinesterase (AChE). The therapy of intoxication with OP-compounds, especially of nerve agents is an extensively investigated. Atropine, standard oximes and diazepam are not satisfactory and it would be advantageous to introduce new compounds, alone or combined with actually used drugs. In this paper two new derivatives of quinuclidinium and imidazolim oximes with atropine were tested in combination with HI-6 and/or diazepam on mice intoxicated with soman and tabun, respectively. All tested compounds were applied intraperitoneally (at 1/4 of their respective LD50 dose) together with atropine (10 mg/kg b.w.) and diazepam (2.5 mg/kg b.w.)one minute after subcutaneous administration of tabun or soman. Each tested oxime applied together with HI-6 gave very good therapeutic effect in soman or tabun poisoning. Therapeutic factor expressed as LD50 of poison with antidote/LD50 of poison without antidote was in the range from 4.8 to 9.4 LD50 of poison. When tested oximes were applied together with HI-6, the survival of all animals was ensured in the range from 3.18 to 5.0 LD50 dose of poison used. However, when tested oximes were combined with diazepam, the therapy was not that efficient as when oximes were combined with HI-6. Quinuclidinium and imidazolium oximes were synthesized at Faculty of Sciences, University of Zagreb.

oximes; tabun; soman; HI-6; diazepam

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