engleski

Structure-activity relationships of new antidotes in therapy of soman poisoning

This paper evaluates and compares antidotal characteristics of new antidotes with regard to their chemical structure. Tests were run on series of imidazolium, quinuclidinium, and pyridinium derivatives with different chains between rings and with different substituents on the rings. The activity of these compounds was determined in vitro on human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7) inhibited by Soman, and in vivo on Soman poisoned mice. We found that the length andthe type of the chain between rings and the type of substituent on the rings significantly influence the in vitro affinity, acute toxicity, and in vivo effectiveness of these antidotes. Imidazolium and pyridinium compounds demonstrated mostly weak reactivating and protective characteristics both in vitro and in vivo. All tested quinuclidinium derivatives were not effective in vitro. However, these compounds were effective in vivo, which indicates that the mechanism of their activity does not involve reactivation and/or protection of AChE in the nervous system.

soman; antidotes; quinuclidinium; imidazolium; oximes; AChE

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