Comparison of the potency of newly developed and currently available oximes to reactivate nerve agent-inhibited acetylcholinesterase in vitro and in vivo.

Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Chemico-Biological Interactions (Impact Factor: 2.97). 01/2006; 157-158:367-8. DOI:10.1016/j.cbi.2005.10.054
Source: PubMed

ABSTRACT Reactivation potency of three newly developed oximes K027, K033 and K048 was tested using standard in vitro and in vivo reactivation tests. K027 and K048 seem to be efficacious reactivators of tabun-inhibited acetylcholinesterase. K033 is sufficient reactivator of cyclosarin-inhibited AChE. However, its potency is poor compared with current "gold standard" oxime HI-6.

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    ABSTRACT: Oximes are well known as acetylcholinesterase reactivators and are used in organophosphorus poisoning to reactivate inhibited acetylcholinesterase. Therapeutically available oximes, namely, pralidoxime (2-PAM), obidoxime, trimedoxime and Hagedorn oxime (HI-6), have no broad-spectrum activity against structurally different kinds of organophosphorus anticholinesterases. The widely used oxime, 2-PAM, is least effective. The focus of the review is to find an oxime that is broad spectrum and superior to the presently available oximes for the treatment of organophosphorus poisoning. Numerous oxime-based reactivators have been synthesized -in laboratories in Croatia, United States of America, Israel and most recently in Czech Republic. Some experimental oximes synthesized in Czech Republic and named as K-series of oximes have been found promising. Among them, K-27 and K-48 have higher or comparable efficacy to all available oximes though it is not effective against all organophosphorus (OP) nerve agents. They are also efficacious in pretreatment protocol for OP anticholinesterases. K-27 oxime is a promising candidate to replace therapeutically available oximes with respect to insecticide/pesticide organophosphorus poisoning. K27 and K48 may be candidates to replace the only approved pretreatment drug, pyridostigmine, in military combat medicine for OP nerve agent. Keywords: K-oximes, K-27 and K-48 oxime, Bispyridinium aldoxime, Acetylcholinesterase reactivators, OPC poisoning.
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