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In this paper, new synthesized oxime derivatives of imidazole 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 test compounds, oximes, that inhibit to 50 % of the AChE activity), acute toxicity (LD 50 ), 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 syntesized oximes were compared and related to their chemical structures. Derivatives of imidazoles demonstrated mostly weak reactivating and protective characteristics, both for the in vitro and in vivo cases. These characteristics were independent 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 erythrocytes. BMR-4 oxime, in combination with atropine sulfate, provided effective protection in vivo (for mice) against 1.8 and 2.2 LD50 of soman. On the contrary, all tested quinuclidine oximes showed very good protection in vivo (for example, BM-1 protects against 4 x 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 telated 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.

3-Carbamoyloxy, 3-hydroxy and 3-oxo quinuclidinium derivatives were synthesized as possible antidotes of organophosphorus poisoning.

The in vitro activity of human erythrocyte acetylcholinesterase (AChE) and protective activity against soman dichlorovos, and propoxur poisoning in male mice (in vivo experiments) were determined by using bis- phenyl imidazolium (2B) and imidazole- quinuclidinium oximes (BM-1). Oxime 2B strongly inhibits the AChE, and has a good reacitvation potency, but weak protective ability, against AChE inhibited by these agents. Oxime BM-1 inhibits weakly AChE and its in vitro activity against inhibited AChE is negligible. In vivo, this oxime is a very good protective agent against inhibitors tested in this paper. BM-1, given with atropine sulphate, provided a 100 % protection in male mice gainsit 4 x LD 50 soman, 11 x LD 50 dichlorovos, and 16 x LD 50 propoxur, respecitvely. The results indicate that in vivo effectiveness of quinuclidinium oxime is not related to its reactivatin or protective potentials for AChe, as shown by the in vitro experiments. The in vivo action of this BM-1 oxime must be attributed to mechanism not yet well defined.

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.

This investigation was aimed at finding out to what extent the nature of the p-CH3 substituent in N-phenyl imidazolium oximes affects the in vitro inhibitory power (IC-50) on human erythrocyte AChE inhibited by soman and in vitro protection against soman. Acute toxicity (LD50)in mice, was determined in vivo as well as the protection against soman intoxication. Four new p-methylphenyl(mono-imidazolium, imidazolium-pyridinium and bis-imidazolium) oximes were prepared and characterized by elemental analysis, IR and proton NMR- spectroscopy. IC-50 values were determined only for BMR-2 and BMR-3 because BMR-1 and BMR-2 provoke

The inhibitory power (IC50), reactivation of soman phosphylated AChE and protection of human erythrocyte AchE against inhibition by soman, were detrmined by applying bis-imidazolium and two pyridinium-imidazolium oximes containing methyl, benzyl, phenyl and 4-fluorophenyl substituents at position 3 of the imidazole ring. The rings were linked with alkylidene, ether and diether chains. The IC-50 values varied from 2x10-8 to 2x10-4 mol/L. The oximes with six C-atoms in the alkylidene chain, except 2B with four C-atoms, showed the highest inhibitory power of all investigated compounds. The type of substituent on the imidazole ring and the length of the chain between rings have a significant influence on the IC-50 of these oximes. It seems that newly synthesized bis- imidazolium oximes are stronger inhibitors than pyridinium-imidazolium compounds. Only compound 2B from the oximes tested is a week inhibitor, has good reactivation potency and protective ability for AchE inhibited by soman. All the other oximes tested have not these properties which can be explained by their strong inhibitory power.