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Effectiveness of imidazole and quinuclidine derivatives on acetyl cholinesterase inhibited by soman in vitro and in vivo

In this paper, new synthesized oxime derivatives of imidazoles and quinuclidines were tested in vitro using human erythrocyte AChE inhibited by soman and in vivo using soman poisoned mice. The inhibitory power (IC50, concentration of the tes compounds, oximes, that inhibit to 50 % of the AChE activity), acute toxicity (LD50), as well as reactivating and protective capacities, with respect to soman-inhibited AChE were tested for each of the synthesized oximes. Antidotal characteristics of the new synthesized oximes were compared and related to their chemical structures. Derivatives of imidazoles demonstrated mostly weak reactivatin and protective characteristics, both for the in vitro and in vivo cases. These characteristics were indempendent of the substituents on N phenyl imidazolium oximes. Of the imidazoles, only BMR-3 oxime strongly reactivated the soman-inhibited AChE (55%), i.e., in vitro, for human erythrocutes. BMR-4 oxime, in combination with atropine sulfate, provided effective protection in vivo (for mice)against 1.8 and 2.2 LD 50 of soman. Ont he contrary, all tested quinuclidine oximes showed very good protection in vivo (for example, BM-1 protects agains 4 LD 50 of soman), but were ineffective in vitro, i.e., against soman-inhibited human erythrocyte AChE. The results indicate that in vivo effectiveness of quinuclidine oximes against soman poisoning is not related to their reactivating or protective potentials for AChE measured in in vitro experiments ; their good protective effect is more likely to be related to other mechanisms of the cholinergic system.

soman ; quinuclidinium oximes ; AcHE

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