title: An evaluation of reactivating and therapeutic efficacy of newly developed oximes (K206, K269) and commonly used oximes (obidoxime, HI-6) in cyclosarin-poisoned rats and mice.
abstract: BACKGROUND
  The ability of currently available reactivators to reactivate cyclosarin is low. The aim of this study was to determine the reactivating and therapeutic efficacy of newly developed oximes (K206, K269) compared with currently available oximes against cyclosarin.
  
  
  METHODS
  Rats and mice received atropine or atropine + oxime intramuscularly (i.m.) before or after an i.m. dose of cyclosarin. Acetylcholine activity levels in blood and tissues were measured to calculate the reactivation efficacy and potency.
  
  
  CONCLUSIONS
  In vivo determined percentage of reactivation of cyclosarin-inhibited blood and tissue acetylcholinesterase (AChE) in poisoned rats showed that the potency of both newly developed oximes (K206, K269) to reactivate cyclosarin-inhibited AChE is comparable with that of obidoxime in blood and diaphragm, but slightly higher than that of obidoxime in brain. Their reactivating efficacy is significantly lower compared with that of the oxime HI-6. K206 and K269 are relatively effective in reducing cyclosarin-induced lethal toxic effects in mice. Their therapeutic efficacies exceed the therapeutic potency of obidoxime but not that of HI-6.
  
  
  CONCLUSIONS
  K206 and K269 are as effective in the reactivation of cyclosarin-inhibited AChE in rats and in the reduction of lethal toxic effects of cyclosarin in mice as obidoxime, but because their reactivating and therapeutic potency is significantly lower than that of HI-6, they are not suitable replacements for the currently available oximes for the treatment of cyclosarin poisoning.
authors.affiliation: Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Jana
authors.initials: J
authors.lastname: Karasova
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Bajgar
mesh_terms: D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D003964:Diaphragm / Q000201:enzymology; D004359:Drug Therapy, Combination; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009768:Obidoxime Chloride / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds; D010091:Oximes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D011041:Poisoning / Q000188:drug therapy / Q000201:enzymology; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: C534465:1-(3-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene; C534466:1-(4-(1-aminohydroxyiminomethyl)pyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; D002802:Cholinesterases; C022870:asoxime chloride; C053914:cyclohexyl methylphosphonofluoridate