Effect of seven newly synthesized and currently available oxime cholinesterase reactivators on cyclosarin-intoxicated rats.
Seven new oxime-based acetylcholinesterase reactivators were compared with three currently available ones (obidoxime, trimedoxime, HI-6) for their ability to lessen cholinesterase inhibition in blood and brain of cyclosarin-treated rats. Oximes were given at doses of 5% their LD(50) along with 21 mg/kg atropine five min before the LD(50) of cyclosarin (120 ug/kg) was administered. Blood and brain samples were collected 30 minutes later. The greatest difference between acetylcholinesterase inhibition in blood of cyclosarin-treated rats was found after administration of HI-6 (40%), compared to 22% for trimedoxime and 6% for obidoxime. Only two of the seven newly synthesized oximes had any effect (K203 at 7%, K156 at 5%). Effective oximes against cyclosarin-inhibited plasma butyrylcholinesterase were HI-6 (42%), trimedoxime (11%), and K156 (4%). The oximes were less effective in brain than in blood, with reactivation values for HI-6 30% against acetylcholinesterase and 10% against butyrylcholinesterase. Values for newly synthesized oximes were less than 10% for K206, K269 and K203.
Karasova
Jana Zdarova
JZ
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Kassa
Jiri
J
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Musilek
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Pohanka
Miroslav
M
Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Novotny
Ladislav
L
Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Kuca
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.|Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.|Department of Chemistry, Faculty of Sciences, J.E. Purkinje University, Horeni 13, 400 96, Usti nad Labem, Czech Republic.
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D001285:Atropine; D000110:Acetylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate