engleski

Interaction of pyridinium oximes K027, K033 and K048 with native and tabun-inhibited human acetylcholinesterase

This study examined the ability of three bispyridinium oximes K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], and K033 [1, 4-bis(2-hydroxyiminomethylpyridinium) butane dibromide] to reactivate tabun-inhibited human erythrocyte AChE. Reversible inhibition of native AChE by these oximes and their protective index of AChE inactivation by tabun were determined as well. Tabun-inhibited AChE was completely reactivated by micromolar concentrations of K027 and K048. The reactivation by K033 reached 50 % after 24 hours. All the oximes were reversible inhibitors of AChE, and dissociation constants were 17 μ M, 73 μ M and 110 μ M for K033, K027 and K048, respectively. All studied oximes protected the enzyme from phosphonylation by tabun by at least factor 2. Our in vitro experiments pointed out K048 and K027 as promising reactivators, while K033 showed promise as a protective agent in tabun poisoning.

Acetylcholinesterase; Antidotes; Inhibition; Protection; Reactivation; Warfare nerve agents

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