Oximes K033 [1,4-bis(2-hydroxyiminomethylpyridinium)
butane dibromide] and K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)
butane dibromide] were tested as pretreatment drugs in
tabun-poisoned mice followed by treatment with
atropine plus K033, K048, K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)
propane dibromide],
TMB-4 [1,3-bis(4-hydroxyiminomethylpyridinium)
propane dibromide] and
HI-6 [(1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride)].
Oxime doses of 25% or 5% of its LD(50) were used for pretreatment 15 min before
tabun-
poisoning and for treatment 1 min after
tabun administration to mice. The best
therapeutic effect was obtained when
oxime K048 (25% of its LD(50)) was used in both pretreatment and treatment with
atropine. This regiment insured survival of all tested animals after the application of 10 LD(50) of
tabun. In addition, since
butyrylcholinesterase (BChE; EC 3.1.1.8) is considered an endogenous bioscavenger of
anticholinesterase compounds and its interactions with
oximes could be masked by AChE interactions, we evaluated kinetic parameters for interactions of tested
oximes with native and
tabun-inhibited human plasma BChE and compared them with results obtained previously for human erythrocyte
acetylcholinesterase (AChE; EC 3.1.1.7). Progressive inhibition of BChE by
tabun was slightly faster than that of AChE. The reactivation of
tabun-inhibited BChE by
oximes was very slow, and BChE binding affinity for
oximes was lower than AChE's. Therefore, BChE could scavenge
tabun prior to AChE inhibition, but fast
oxime-assisted reactivation of
tabun-inhibited AChE or protection of AChE by
oxime against inhibition with
tabun would not be obstructed by interaction between BChE and
oximes.