In Vitro Reactivation of Acetylcholinesterase Inhibited by Cyclosarin Using Bisquaternary Pyridinium Aldoximes K005, K033, K027 and K048

Abstract

We have tested four new bisquaternary pyridinium acetylcholinesterase (AChE; EC 3.1.1.7) reactivators – K005 (1,3–bis(2–hydroxyiminomethylpyridinium) propane dibromide), K033 (1,4–bis(2–hydroxyiminomethylpyridinium) butane dibromide), K027 (1–(4–hydroxyiminomethylpyridinium)-3–(4–carbamoylpyridinium) propane dibromide) and K048 (1–(4–hydroxyiminomethylpyridinium)-4–(4–carbamoylpyridinium) butane dibromide) as the potential reactivators of AChE inhibited by cyclosarin. Their reactivation potencies were studied using standard in vitro reactivation test. Rat brain homogenate was used as the source of the enzyme. Oxime K033 seems to be the most potent reactivator of cyclosarin-inhibited AChE. Its reactivation potency is significantly higher than the efficacy of all other tested AChE reactivators.

Keywords

• Cyclosarin
• In vitro
• Reactivation
• Inhibition
• Acetylcholinesterase
• K005