Pralidoxime iodide (2-PAM), an
antidote approved for the reactivation of inhibited
acetylcholinesterase (AChE) in
organophosphate poisoning, dose-dependently hydrolyzed an
acetylthiocholine iodide (ASCh). The AChE (0.3 U) activity inhibited by
VX analog (ENMP, 0.1 microM) increased to approximately 200% of normal levels after a dosage of 5 mM
2-PAM (control 0.132+/-0.012 U/ml, 5 mM 0.253+/-0.026 U/ml). This result indicates that
2-PAM produced a
thiocholine from the ASCh by hydrolysis. High-performance liquid chromatography (HPLC) analysis was then performed to further clarify the hydrolysis of ASCh with
2-PAM. It was clear that
2-PAM was converted to acetylated
2-PAM with
acetic acid produced from ASCh by hydrolysis. Next, we tried to compare this
esterase-like activity of
2-PAM with that of
obidoxime, which is known as a strong reactivator of inhibited AChE, and with
diacetylmonoxime, known as a weak reactivator. All of these
oximes showed
esterase-like activity, and their strengths were consistent with those of known reactivators of inhibited AChE. These results indicate that a great deal of the data obtained previously with ASCh relating to the effects of
oximes must be rechecked. It is clear that
oximes easily hydrolyze ASCh. We therefore strongly caution that the method of determining AChE activity with ASCh is not suitable for examining the effects of
oximes.