Stereospecificity of Antidotes and Their Mechanism of Action in Intoxications with Organophosphorus Anticholinesterases.
Final rept. 1 Feb 87-31 Aug 90,
KAROLINSKA INST STOCKHOLM (SWEDEN) DEPT OF TOXICOLOGY
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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. 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. 2 Influence of cholinergic substances on the functional muscarinic-receptor pool. 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.