The evaluation of the neuroprotective effects of bispyridinium oximes in tabun-poisoned rats.
Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to the group of highly toxic organophosphorus compounds that may be used as chemical warfare agents for military as well as terrorist purposes. Tabun differs from other highly toxic organophosphates by the fact that commonly used antidotes are not able adequately to prevent tabun-induced acute toxic effects. The neuroprotective effects of four bispyridinium oximes (K075, trimedoxime, HI-6, obidoxime) in combination with atropine on rats poisoned with tabun at a sublethal dose (150 microg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h and 7 d following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 7 d following challenge. Trimedoxime combined with atropine was the most effective antidote in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Due to its neuroprotective effects, trimedoxime may be considered to be more suitable oxime for the antidotal treatment of acute tabun exposure than currently used oximes (obidoxime, HI-6) and the newly synthesized oxime K075.
Kassa
Jiri
J
Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Karasova
Jana
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000506:poisoning; D002800:Cholinesterase Inhibitors / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D010755:Organophosphates; D010091:Oximes; D001285:Atropine; C009374:tabun