A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase

BMC Pharmacology and Toxicology

Eugenie Nepovimova¹  Kamil Musilek¹  Jana Zdarova-Karasova¹  Daniel Jun¹  Ondrej Soukup¹  Martina Hrabinova¹  Kamil Kuca¹  Teodorico C. Ramalho²  Tanos C. C. Franca²  John Mikler³  Alexandre A. De Castro⁴  Elaine F. F. Da Cunha⁴  Martin Valis⁵ 

[1] Biomedical Research Center, University Hospital Hradec Kralove;Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove;Defence Research and Development Canada - Suffield Research Centre, Department of National Defence, Suffield;Department of Chemistry, Federal University of Lavras;Neurology Clinic, University Hospital Hradec Kralove;

关键词: Antidotes;    Chemical warfare agents;    Poisoning;    Treatment;    Reactivator;    Oxime;   

DOI  :  10.1186/s40360-018-0196-3

来源: DOAJ

【 摘 要 】

Abstract Background Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. Methods To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k r) of 2142 min− 1. M− 1, which was 51 times higher than that obtained for obidoxime (k r = 42 min− 1. M− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.

【 授权许可】

Unknown