In Search of An Ideal Bioscavenger for Organophosphate Chemical Warfare Agent Toxicity

摘要

Current antidotal regimens for OP poisoning consist of a combination of pretreatment with spontaneously reactivating AChE (EC 3.1.1.7) inhibitor, i.e., carbamates, (pyridostigmine bromide), to protect it from irreversible inhibition by OP compounds, and post exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent post-exposure incapacitation, convulsions, seizures, performance decrements, or in many cases permanent brain damage (Dirnhuber, et al., 1979; McLeod, 1985; Dunn, et al., 1989). These symptoms are commonly observed in experimental animals and are likely to occur in humans. An anticonvulsant drug diazapam was included as a treatment to minimize convulsions, thereby minimizing the risk of permanent brain damage.