Kuca_2006_Mil.Med.Sci.Lett_75_37

Antidotal treatment of nerve agent poisonings consists of anticholinergics (atropine mainly) and acetylcholinesterase (AChE) reactivators (pralidoxime, obidoxime, methoxime or HI-6). Due to the fact that currently available AChE reactivators are not able to reactivate AChE inhibited by all potential nerve agents, the development of new AChE reactivators still continues. For this purpose, the understanding of relationship between structural factors and their influence on the reactivation potency is useful. Especially, presence and number of functional oxime groups, presence and number of quaternary nitrogens, lentgh and shape of the connecting chain are discussed. Eleven AChE reactivators differing in the length and shape of the connecting chain were tested by in vitro methods in this work. Sarin was used as a representative of the nerve agent family. As resulted, the highest reactivation potency was achieved for trimedoxime (54 %) and oxime K074 (54 %). This reactivation potency was, however, obtained at concentration (10-3 M) that is not attainable for human use. Oximes TO 047 and TO 033 seem to be the most potent AChE reactivator tested in this study at concentration (10-5 M) that is relevant for human use.