J Appl Biomed 13:299-304, 2015 | DOI: 10.1016/j.jab.2015.07.002

A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K920, K923) with the oxime K203 and trimedoxime in tabun-poisoned rats and mice

Jiri Kassa^*, Vendula Sepsova, Anna Horova, Kamil Musilek

Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

The potency of two novel oximes (K920, K923) to reactivate tabun-inhibited acetylcholinesterase and to reduce acute toxicity of tabun was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited peripheral acetylcholinesterase (diaphragm) and central acetylcholinesterase (brain) in tabun-poisoned rats showed that the reactivating efficacy of both newly developed oximes is lower than the reactivating potency of the oxime K203 and trimedoxime. The therapeutic efficacy of both newly developed oximes roughly corresponds to their weak reactivating efficacy. Their potency to reduce acute toxicity of tabun in mice was lower compared to the oxime K203 and trimedoxime. All differences in reactivating efficacy of oximes and different protective ratios were found for selected doses of oximes used in this study. Based on the results obtained, we can conclude that the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning. The conclusion is only relevant for the experimental animals used in this study because of remarkable species differences in reactivating properties of oximes.

Keywords: Tabun; Acetylcholinesterase; Oximes; Rats; Mice

Received: June 3, 2015; Revised: July 21, 2015; Accepted: July 23, 2015; Published: November 1, 2015  Show citation