Stereospecificity of Antidotes and Their Mechanism of Action in Intoxicationswith Organophosphorus Anticholinesterases

摘要

Our program during the grant period has mainly been concerned with studies on:(1) Effect of antidotes such as l-hyoscyamine and atropine, diazepam, and Hl-6, separately and in combinations, on the dynamics of acetylcholine, and (2) Influence of cholinergic substances on the functional muscarinic-receptor pool. We found that diazepam counteracts the increased rate of synthesis and release of acetylcholine induced by l-hyoscyamine. The addition of diazepam to conventional atropine-oxime therapy is therefore more effective in cases of organophosphate intoxications. Soman-intoxicated mice pretreated with the three-drug combination show no cholinergic symptoms and have a normal turnover of acetylcholine. Diazepam was found to decrease the size of the active receptor pool, which may lead to the observed effect on the dynamics of acetylcholine and choline.