Antagonism of Phospholine (Echothiophate) Iodide ∗ by Certain Quaternary Oximes

Summary

Protopam (pralidoxime) Chloride (or Iodide) and TMB4 (1, 1′-trimethyl-ene-bis(4-formylpyridinium bromide) dioxime) when injected intraperitoneally in the mouse at 50% of LD₅₀, raise the intraperitoneal lethal dose of anticholinesterase, Phospholine (echothiophate) Iodide, by factors of 50 and 280 respectively. When the same oximes are given orally 30 to 60 minutes before Phospholine the intraperitoneal LD₅₀ is increased by factors of 23 and 450. Graphs relating log dose of oxime and log dosage ratio of Phospholine are linear over a considerable range. The therapeutic indices for arbitrary increase of 10 times in LD₅₀ of Phospholine are 23 and 9 for Protopam and 114 and 120 for TMB4 by oral and intraperitoneal administration respectively. The possible nature of the antagonism is discussed.