title: A comparison of the potency of newly developed oximes (K005, K027, K033, K048) and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited rat brain acetylcholinesterase by in vitro methods.
abstract: The potency of newly developed and currently used oximes to reactivate sarin-inhibited acetylcholinesterase was evaluated using in vitro methods. A rat brain homogenate was used as a source of acetylcholinesterase. Significant differences in reactivation potency among all tested oximes were observed. Although the ability of newly developed oximes to reactivate sarin-inhibited acetylcholinesterase does not reach the reactivating potency of the oxime HI-6, the oxime K033 seems to be a more efficacious reactivator of sarin-inhibited acetylcholinesterase than other currently available oximes (pralidoxime, obidoxime) at concentrations (10(-5)-10(-4)M) corresponding to recommended doses in vivo. The results of our study also confirm that the reactivation potency of the tested reactivators depends on many factors, such as (1) the number of pyridinium rings, (2) the number of oxime groups and their position, and (3) the length and the shape of the linkage bridge between pyridinium rings.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, Hradec Králové, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Cabal
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D008297:Male; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D010091:Oximes; D012524:Sarin; D000110:Acetylcholinesterase