Rosenberg_1960_Biochem.Pharmacol_3_212

Pyridine-2-aldoxime methiodide (PAM) injected in amounts of from 25 to 150 mg/kg from 0.5 to 1.5 hr after 0.15 mg/kg paraoxon caused a significant increase in the cholinesterase levels of cerebral cortex, pons, cerebellum, region of area postrema in medulla, and the remainder of the medulla of rabbits killed 3 hr after the injection of paraoxon. Reactivation seemed most marked in the pons, region of area postrema and the remainder of the medulla. Similar results were obtained when rabbits were killed 24 hr after paraoxon, and there appeared to be no difference whether the first dose of PAM was given 1 or 5 hr after the inhibitor. A chloroform extraction procedure was used which appears capable of removing at least some of the extracellular paraoxon present in the brain tissue and uncombined with the enzyme at the time of sacrifice of the rabbits. It is concluded that sufficient amounts of PAM are able to penetrate into the brain to cause marked reactivation of inhibited cholinesterase. Possible reasons are discussed why other workers have not observed in vivo reactivation of brain cholinesterase by PAM.