Bovine erythrocyte acetylcholinesterase inhibited by 1,2,2'-trimethylpropyl methylphosphonofluoridate (soman) is reactivated rapidly but incompletely by 1 mM of the bispyridinium mono-oximes HI-6, HS-6, HGG-12 and HGG-42 (pH 7.5, 25°). These oximes, especially HI-6 and HS-6, show a higher reactivating potency than conventional reactivators, like P2S, obidoxime or TMB4. The incomplete reactivation is studied in more detail with HI-6, which is found to be the most potent reactivator. Rapid reactivation and aging take place in the presence of the oxime (10–70 μM). The reactions are not consistent with a minimum scheme involving simultaneous aging of the inhibited enzyme and reactivation and aging of an inhibited enzyme-oxime complex. The formation of aged enzyme can be described as a first-order process. The formation of reactivated enzyme proceeds in a more complicated manner. HI-6 appears to have no effect on aging of the soman-inhibited enzyme. It is concluded that HI-6, being able to compete with the rapid aging of soman-inhibited acetylcholinesterase, has an extremely high reactivating potency, on which the therapeutic effect of the oxime is based.
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