Acetylcholinesterase prophylaxis against organophosphate toxicity

Fetal bovine serum acetylcholinesterase (FBS-AChE) protected mice from multiple LD50 doses of organophosphorus (OP) nerve agents. Mice were injected intraperitoneally (ip) with up to 3.3 mg (11,000 U) of FBS-AChE which exhibited a relatively long serum half-life and appeared well tolerated. The enzyme protected mice from the OP ethyl-S-2-diisopropylamino-ethylmethylphosphonothiolate (VX) with a stoichiometry equal to approximately 2 moles of enzyme active site per mole of VX. FBS-AChE, at a lower enzyme OP ratio, protected mice from 2 LD50s of the nerve agent methylphosphonofluoridic acid 1,2,2,-trimethylpropyl ester (soman) when used in conjunction with atropine and 2[(hydroxyimino)methyl]-1-methylpyridinium chloride. It is concluded that sequestration of highly toxic OPs by administration of AChE occurs in mice and suggests a new approach to treatment of OP intoxication.