Antagonism of Phospholine (Echothiophate) Iodide by Certain Quaternary Oximes

Abstract

Antagonism of Phospholine (ethothiophate) Iodide by Protopam (pralidoxime) Iodide (2-PAM, 2-pyridine aldoxime methiodide) or TMB4 (1, l[image]-trimethylene-bis(4-formylpyridinium bromide)dioxime) was investigated by intraperitoneal injection and oral administration in the mouse. In the former case the anticholinesterase and the oxime were given simultaneously, while in the latter, the oxime was given at various time intervals beforehand. Protopam and TMB4, when injected intraperitoneally, raise the intraperitoneal lethal dose of Phospholine by factors of 50 and 280 respectively. When the same oximes are given orally 30 to 60 minutes before intraperitoneal Phospholine the LD50 is increased by factors of 23 and 450. Therapeutic indices for an arbitrary increase of 10 times in the LD50 of Phospholine are 23 and 9 for Protopam and 114 and 120 for TMB4 by oral and intraperitoneal administration respectively. Because of the apparent parallelism among the dosage mortality curves and the linearity over a considerable range of the relationship between log dosage ratio of Phospholine (with and without oxime) and log dose of oxime it is suggested that the antagonism is probably competitive.