Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005, 149(1):75-82 | DOI: 10.5507/bp.2005.008

New quaternary pyridine aldoximes as casual antidotes against nerve agents intoxications

Kamil Kuča^a, Lucie Bartošová^a, Daniel Jun^a,b, Jiří Patočka^a,c, Jiří Cabal^a, Jiří Kassa^a, Gabriela Kunešová^a

^a Department of Toxicology, Faculty of Military Health Sciences, Třebešská 1575, Hradec Králové, Czech Republic

^b Department of Pharmaceutical Botany and Ecology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

^c Department of Radiology and Toxicology, Faculty of Health and Social Studies, South Bohemia University, České Budějovice, Czech Republic

In this work, the ability of four newly synthesized oximes - K005 (1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide), K027 (1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide), K033 (1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide) and K048 (1-(4-hydroxyiminomethylpyridinium)-4-(4- carbamoylpyridinium) butane dibromide) to reactivate acetylcholinesterase (AChE, EC 3.1.1.7) inhibited by nerve agents is summarized. Reactivation potency of these compouds was tested using standard in vitro reactivation test. Tabun, sarin, cyclosarin and VX agent were used as appropriate testing nerve agents. Rat brain AChE was used as a source of the enzyme. Efficacies of new reactivators to reactivate tabun-, sarin-, cyclosarin- and VX-inhibited AChE were compared with the currently used AChE reactivators (pralidoxime, obidoxime and HI-6). Oxime K048 seems to be promising reactivator of tabun-inhibited AChE. Its reactivation potency is significantly higher than that of HI-6 and pralidoxime and comparable with the potency of obidoxime. The best reactivator of sarin-inhibited AChE seems to be oxime HI-6. None of the new AChE reactivators reached comparable reactivation potency. The same results were obtained for cyclosarin-inhibited AChE. However, oxime K033 is also potent reactivator of AChE inhibited by this nerve agent. In the case of VX inhibition, obidoxime and new oximes K027 and K048 seem to be the best AChE reactivators. None from the currently tested AChE reactivators is able to reactivate AChE inhibited by all nerve agents used and, therefore, the search for new potential broad spectrum AChE reactivators is needed.

Keywords: Acetylcholinesterase, Inhibition, Reactivation, HI-6, Pralidoxime, Obidoxime, Reactivator, In vitro

Received: May 10, 2005; Accepted: June 7, 2005; Published: July 1, 2005  Show citation