A comparison of the reactivating and therapeutic efficacy of two novel oximes K378 and K458 with currently available oximes in rats and mice poisoned with sarin

The ability of two novel oximes K378 and K348 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. Both new potential oxime reactivators were chosen for this study based on the data obtained during the extensive work on oximes development, from structure-activity relationship studies and in vitro evaluation of their ability to reactivate acetylcholinesterase inhibited by organophosphorus compounds. In vivo determined percentage of reactivation of sarin-inhibited rat blood and brain acetylcholinesterase showed that the potency of both novel oximes K378 and K458 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to low reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be efficient reactivator of sarin-inhibited acetylcholinesterase in the peripheral compartment. While the oxime HI-6 was able to reduce the acute toxicity of sarin more than three times, both novel oximes decreased the acute toxicity of sarin less than two times. Based on the results, we can conclude that reactivating and therapeutic efficacy of both novel oximes K378 and K458 are significantly lower compared to the oxime HI-6 and, therefore, it is not suitable to replace the oxime HI-6 for the antidotal treatment of acute sarin poisoning. (C) 2014 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.