The lack of efficacy of combined therapies, involving a cholinolytic drug and an oxime, is reviewed. Problems include rapid aging of the phosphylated acetylcholinesterase, poor reactivation of nonaged inhibited enzymes (oxime resistancy), and the predominant effect of soman on the central nervous system. Species differences and the persistence of soman in depots complicate treatment. Reactivation of only a few percent of the total amount of functional cholinesterase can save life, so enzyme aging is not serious. Oxime resistance is overcome by oximes which effectively penetrate the blood brain barrier. These oximes also have antidotal effects not based on enzyme reactivation.
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