In this in vitro study, high-performance liquid chromatography (HPLC) was used to determinate the penetration of 30 acetylcholinesterase (AChE) reactivators through the blood-brain barrier (BBB). According to our method, monoquaternary AChE reactivators were found to be able to penetrate the BBB. In addition to molecular structure, molecular weight appears to be an important factor for passive transport of oximes through the BBB. For bisquaternary reactivators, the connecting linker plays a key role in the ability to penetrate into the central nervous system (CNS): simple, short linkers tend to facilitate permeation. The location of groups on the pyridine ring also influences passive transport into the brain; the optimum position of the oxime group was found to be position four (para) and substitution of the oxime group on the pyridine ring by carbamoyl or amidoxime group markedly decreased penetration of AChE reactivators into the CNS.
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