Maximal inhibition of cholinesterase in the central nervous system.

In experiments on mice treated with pralidoxime iodide (pyridine-2-aldoxime methiodide; PAM) and atropine, the cholinesterase activity in the brain was assayed after poisoning with very high doses of organophosphorous anticholinesterases. Acetylcholine was added to the buffer solution in which the brains were homogenized. This precaution reduced the combination between free inhibitor present in the tissue and active enzyme, and the cholinesterase activity found was below 0.5% of controls. When the experimental data were corrected for spontaneous reactivation in vitro during incubation, the calculated activities in vivo were even less. It is concluded that mice can survive complete inactivation of the cholinesterase in the central nervous system, if enough atropine is given to protect the animals against the toxic effects of the accumulating acetylcholine.