Neuroprotective effects of currently used antidotes in soman-poisoned rats

The neuroprotective effects of antidotes (atropine, obidoxime, obidoxime/at ropine mixture) on rats poisoned with soman at a sublethal dose (54 mug/kg, im, 80% of LD50 value) were studied. The soman-induced neurotoxicity was m onitored using a functional observational battery (FOB) and an automatic me asurement of motor activity. The neurotoxicity of soman was monitored at 24 h and 7 days following soman challenge. The results indicate that obidoxim e alone is not able to protect the rats from the lethal effects of soman. T hree 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 antidota l treatment for the elimination of soman-induced neurotoxicity in the case of sublethal poisonings, although the antidotal mixture is significantly le ss effective than atropine alone because obidoxime can counteract the benef icial effects of atropine. Obidoxime appears to be practically ineffective to diminish soman-induced neurotoxicity. The neuroprotective effects of ant idotal mixture consisting of atropine and obidoxime depend on the antimusca rinic 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 p oisonings. (C) 2000 Elsevier Science Inc. All rights reserved.