Accession Number : ADA243678

Title :   Stereospecificity of Antidotes and Their Mechanism of Action in Intoxications with Organophosphorus Anticholinesterases.

Descriptive Note : Final rept. 1 Feb 87-31 Aug 90,

Corporate Author : KAROLINSKA INST STOCKHOLM (SWEDEN) DEPT OF TOXICOLOGY

Personal Author(s) : Holmstedt, Bo. ; Karlen, Bo ; Nordgren, Ingrid ; Palmer, Lena

Report Date : 28 FEB 1991

Pagination or Media Count : 86

Abstract : 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.

Descriptors :   ACETYLCHOLINE, ANTIDOTES, ATROPINE, CHOLINERGIC NERVES, CHOLINES, CHOLINESTERASE INHIBITORS, DIAZEPAM, DYNAMICS, INTOXICATION, ORGANIC PHOSPHORUS COMPOUNDS, ORGANOPHOSPHATES, RATES, SENSE ORGANS, SIGNS AND SYMPTOMS, SYNTHESIS.

Subject Categories : Toxicology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE