The evaluation of neuroprotective efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin-poisoned rats.
The neuroprotective effects of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with cyclosarin were studied. The cyclosarin-induced neurotoxicity was monitored using a functional observational battery at 24 h and 7 days following cyclosarin challenge. The results indicate that the oxime HI-6 combined with atropine seems to be the most effective antidote for a decrease in cyclosarin-induced neurotoxicity. Both newly developed oximes (K074, K075) as well as obidoxime are also able to counteract cyclosarin-induced acute neurotoxicity, but their neuroprotective potency is significantly lower compared with the oxime HI-6. Therefore, the oxime HI-6 is still the most suitable oxime for the antidotal treatment of acute poisonings with cyclosarin due to its neuroprotective as well as reactivating efficacy.
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Jiri
J
Kassa
Jana
J
Karasova
Libor
L
Vasina
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology* / Q000627:therapeutic use; D001341:Autonomic Nervous System / Q000187:drug effects; D002073:Butanes / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009768:Obidoxime Chloride / Q000494:pharmacology; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012677:Sensation / Q000187:drug effects; D013997:Time Factors
C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; D000931:Antidotes; D002073:Butanes; D002801:Cholinesterase Reactivators; C518856:K075 compound; D018696:Neuroprotective Agents; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; D000110:Acetylcholinesterase; C022870:asoxime chloride; C053914:cyclohexyl methylphosphonofluoridate