MECHANISM OF THE ANTAGONISM BY PRALIDOXIME AND 1,1‐TRIMETHYLENEBIS(4‐HYDROXYIMINOMETHYLPYRIDINIUM) OF THE ACTION OF ECHOTHIOPHATE ON THE INTESTINE

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Abstract
Pralidoxime chloride (pyridine-2-aldoxime methochloride; Protopam Chloride) and 1,1′-trimethylenebis(4-hydroxyiminomethylpyridinium bromide) (TMB-4) antagonize the spasm of the isolated or intact small intestine of the rabbit caused by the anticholinesterase, echothiophate iodide (S-2-dimethylaminoethyl OO-diethyl phosphorothiolate methiodide; Phospholine Iodide). In vitro, both oximes also antagonize the spasm caused by acetylcholine. The quantitative relationships have been studied in comparison with the activity of atropine against echothiophate and acetylcholine. Echothiophate-treated intestine which is subjected to a concentration of oxime sufficient to cause 100% restoration of function (but not cholinesterase reactivation) will go back into spasm on washing out both drugs. Strips treated with a high concentration of oxime, sufficient to cause 100% reactivation of cholinesterase, exhibit normal control tone and motility after washing. It is concluded that pralidoxime and 1,1′-trimethylenebis(4-hydroxyiminomethylpyridinium bromide) have an anticholinergic action as well as the ability to reactivate cholinesterase and that this action plays a significant part in the initial recovery of function under the conditions of these experiments.

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