The Influence of Oxime Selection on the Efficacy of Antidotal Treatment of Soman-Poisoned Rats

Abstract

1. The influence of some acetylcholinesterase reactivators (HI-6, obidoxime, pralidoxime) on the efficacy of antidotal treatment to eliminate soman-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 × LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2. Obidoxime or pralidoxime in combination with atropine were insufficient to enable soman-poisoned rats to survive for 2 hours when given 1 minute after the administration of soman. 3. On the other hand, the ability of the oxime HI-6 in combination with atropine to prevent soman-induced alteration of respiration and circulation was significantly higher. Some rats treated with HI-6 in combination with atropine were fully protected against the lethal toxic effects of soman within 2 hours following soman administration. 4. Our findings confirm that the oxime HI-6 seems to be a much more suitable and efficacious acetylcholinesterase reactivator for the antidotal treatment of severe acute soman-induced poisoning than currently used obidoxime or pralidoxime.

Comparison of Effects of Different Antidotes on Tabun-Induced Cognitive Impairment in Rats Using Water Maze

“…From the cognitive functions point of view, we have to speculate about the role of atropine as a part of used therapy, because it was published that atropine can affect the ability to search goal platform in rodents (4,8), nevertheless, atropine is considered to be integral component of antidotal treatment in the case of organophosphate poisoning (13,14,28,33).…”

Comparison of Changes in Ache Activity in the Brain of the Laboratory Rat After Soman and Tabun Intoxication

“…However, the course of intoxication is more serious in the case of soman intoxication due to its fast dealkylation of enzyme-inhibitor complex. For this reason soman remains the focus of interest of toxicologists 6 . In our next experiments we want to study the situation after using antidotes and to quantify AChE activity 9,10 .…”

“…Acetylcholinesterase is localized in erythrocytes, muscle cells and in nerve cells. Inhibition of AChE leads to accumulation of acetylcholine and the inhibited enzyme undergoes only slow spontaneous reactivation 1,[4][5][6] .…”

Potency of Five Structurally Different Acetylcholinesterase Reactivators to Reactivate Human Brain Cholinesterases Inhibited by Cyclosarin

“…Pralidoxime, an AChE reactivator commercially available in the United States, is considered to have insufficient efficacy against certain nerve agents, such as soman (due to the short aging half-life of 2 to 10 minutes) and cyclosarin (12,13). Obidoxime, another commercially available AChE reactivator, is not able to reactivate cyclosarin-inhibited AChE and there are several studies describing adverse effects after its administration (14)(15)(16).…”