Neuroprotective effects of currently used antidotes in tabun-poisoned rats.
The neuroprotective effects of antidotes (atropine, pralidoxime/atropine, obidoxime/atropine and HI-6/atropine mixtures) on rats poisoned with tabun at a lethal dose (220 microg/kg intramuscularly; 100% of LD50 value) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 hr and 7 days after tabun challenge. The results indicate that atropine alone is not able to protect the rats from the lethal effects of tabun. Three non-treated tabun-poisoned rats and one tabun-poisoned rat treated with atropine alone died within 24 hr. On the other hand, atropine combined with all tested oximes allows all tabun-poisoned rats to survive at least 7 days following tabun challenge. Obidoxime combined with atropine seems to be the most effective antidotal treatment for the elimination of tabun-induced neurotoxicity in the case of lethal poisoning among tested antidotal mixtures. The antidotal mixture consisting of atropine and HI-6 is significantly less effective than the combination of atropine with obidoxime in the elimination of tabun-induced neurotoxicity in rats at 24 hr following tabun challenge. Pralidoxime in combination with atropine appears to be practically ineffective to decrease tabun-induced neurotoxicity at 24 hours as well as 7 days following tabun poisoning. Due to its neuroprotective effects, obidoxime seems to be the most effective and most suitable oxime for the antidotal treatment of acute tabun exposure among currently used oximes. Thus, the replacement of obidoxime by a more effective acetylcholinesterase reactivator for soman poisoning, the oxime HI-6, can to a small extent diminish the neuroprotective efficacy of antidotal treatment in the case of acute tabun poisonings.
Kassa
Jirí
J
Purkyne Military Medical Academy, 500 01 Hradec Králové, Czech Republic. kassa@pmfhk.cz
Krejèová
Gabriela
G
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009768:Obidoxime Chloride / Q000494:pharmacology / Q000627:therapeutic use; D062025:Organophosphate Poisoning; D010755:Organophosphates / Q000037:antagonists & inhibitors; D010091:Oximes; D011220:Pralidoxime Compounds / Q000494:pharmacology / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D000931:Antidotes; D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; C022870:asoxime chloride; C028797:pralidoxime; C009374:tabun