Neuroprotective effects of currently used antidotes in soman-poisoned rats.
The neuroprotective effects of antidotes (atropine, obidoxime, obidoxime/atropine mixture) on rats poisoned with soman at a sublethal dose (54 microg/kg, im, 80% of LD(50) value) were studied. The soman-induced neurotoxicity was monitored using a functional observational battery (FOB) and an automatic measurement of motor activity. The neurotoxicity of soman was monitored at 24 h and 7 days following soman challenge. The results indicate that obidoxime alone is not able to protect the rats from the lethal effects of soman. Three soman-poisoned rats treated with obidoxime alone died within 24 h. On the other hand, atropine alone or combined with obidoxime allows all soman-poisoned rats to survive within 7 days following soman challenge. Atropine alone and combined with obidoxime seems to be relatively effective antidotal treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings, although the antidotal mixture is significantly less effective than atropine alone because obidoxime can counteract the beneficial effects of atropine. Obidoxime appears to be practically ineffective to diminish soman-induced neurotoxicity. The neuroprotective effects of antidotal mixture consisting of atropine and obidoxime depend on the antimuscarinic effects of atropine only. Thus, the replacement of obidoxime by more effective acetylcholinesterase (AChE) reactivators is necessary to increase the neuroprotective efficacy of antidotal treatment in the case of soman poisonings.
Kassa
J
J
Purkyne Military Medical Academy, PO Box 35/T, 500 01, Hradec Králové, Czech Republic. kassa@pmfhk.cz
Koupilová
M
M
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009768:Obidoxime Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D009768:Obidoxime Chloride; D001285:Atropine; D012999:Soman