Acta Pharm. 51 (2001) 1-9
The paper describes a test of antidotal efficiency of compounds 1-8 containing only imidazolium, only quinuclidinium, or both, and bis-imidazolium rings with various substituents (oxo, hydroxy, carbamoyl, and phenyl), on mice poisoned with soman or tabun. The results were expressed as the therapeutic factor (TF), therapeutic dose (TD), and the ratio between dead and injected animals. Imidazolium-quinuclidinium compounds containing oxo (3 and 4) or carbamoyl groups (compounds 5 and 6) and bis-imidazolium compound with phenyl groups (8) were more effective than hydroxy (1 and 2) and mono-imidazolium (7) derivatives tested in soman poisoning. The therapeutic effect was better in soman than in tabun poisoning. The best therapeutic effect was obtained with compounds 6 and 8, which were further tested in combination with HI-6 and/or diazepam. Compounds 6 or 8 combined with HI-6 had a very good therapeutic effect, but they were not that efficient in combination with diazepam. Compound 6 and HI-6 were tested in the pretreatment and therapy of soman poisoning. HI-6 showed higher efficiency in pretreatment, which was not time-dependent. Compound 6 was more efficient in the therapy than HI-6 and the antidotal effect of each compound was better when applied immediately after soman poisoning. Combined pretreatment and therapy within 10 min (before and after poisoning) yielded better results than pretreatment or therapy alone.
Keywords: acethylcholinesterase, antidotes, oximes, imidazolium, quinuclidinium, soman, tabun