A comparison of neuroprotective efficacy of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in tabun-poisoned rats.
The neuroprotective effects of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% LD(50)) were studied. The tabun-induced neurotoxicity was monitored by using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 hours and 7 days following tabun challenge. The results indicate that K203 and obidoxime in combination with atropine allow all tabun-poisoned rats to survive within 7 days following tabun challenge, while 2 nontreated tabun-poisoned rats and 1 tabun-poisoned rat treated with K206 or HI-6 in combination with atropine died within 7 days. Only one of the newly developed oximes (K203) combined with atropine seems to be effective for a decrease in tabun-induced neurotoxicity within 24 hours after tabun sublethal poisoning, although it is not able to eliminate tabun-induced neurotoxicity completely. On the other hand, the neuroprotective efficacy of commonly used oximes (obidoxime and HI-6), as well as one of the new synthesized oximes (K206), is significantly lower in comparison with K203, according to the number of eliminated tabun-induced neurotoxic signs at 24 hours after tabun challenge. Due to its neuroprotective effects, K203 appears to be a suitable oxime for the antidotal treatment of acute tabun poisonings.
Kassa
Jiri
J
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Karasova
Jana
J
Vasina
Libor
L
Bajgar
Jiri
J
Kuca
Kamil
K
Musilek
Kamil
K
D000818:Animals; D002619:Chemical Warfare Agents / Q000009:adverse effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D009768:Obidoxime Chloride / Q000627:therapeutic use*; D010755:Organophosphates / Q000009:adverse effects*; D009943:Organophosphorus Compounds / Q000009:adverse effects; D010091:Oximes / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018696:Neuroprotective Agents; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D009768:Obidoxime Chloride; C009374:tabun