Structural factors influencing potency of currently used acetylcholinesterase reactivators for treatment of cyclosarin intoxications.
Cyclosarin is one member of nerve agent family. Recent treatment of intoxications by organophosphorus compounds, such as nerve agents or pesticides, consists of rapid administration of anticholinergics and AChE reactivators. Owing to the threat of terroristic use of these compounds during last years, improvement of antidotal therapy still continues. As the part of the development of new antidotes, many new AChE reactivators were synthesized and currently some of them are under consideration for introducing them to the medical practice. Their biological activity depends, as in the case of other drugs, on their chemical structure, which affects their pharmacokinetics (adsorption, distribution, metabolism and excretion) and pharmacodynamics. In this review, we would like to discuss relationship between structure of currently available AChE reactivators and their potency to reactivate cyclosarin-inhibited AChE. All outlined structural factors presented in this work should be helpful for the design of new generation of reactivators of cyclosarin-inhibited AChE.
Kuca
Kamil
K
Centre of Advanced Studies and Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Jun
Daniel
D
Bajgar
Jiri
J
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002801:Cholinesterase Reactivators / Q000737:chemistry* / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000633:toxicity*; D013329:Structure-Activity Relationship
D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate