A Comparison of the Antimuscarinic Properties of Aprophen with Those of Some Other Anticholinergic Drugs

摘要

Apparent dissociation constants (Ki) for the interaction of benactyzine, aprophen and atropine with the muscarinic cholinoceptor were determined in the brain (striatum and pons-medulla) and ileum of the guinea pig by competition with (H3)-quinuclidinyl benzilate (QNB) in a direct binding assay. Corresponding dissociation constants in the atrium were determined by antagonism of acetylcholine-induced contractions. In all regions studied, aprophen and benactyzine (which are closely related structurally) were approximately equi-effective, based on their Ki values, and about 1/4 as effective as atropine. Hyoscine and the glycollate T3436 were also studied in the atrium and found to be more potent muscarinic antagonists than atropine. Values of Ki were in the nanomolar range. For any one antagonist, significant differences were observed between Ki values for different regions. Concentrations of aprophen in the millimolar range were necessary for it to have any effect on the kinetics of acetylcholinesterase. The effects of aprophen on the enzyme were similar to those previously reported for benactyzine (Dawson and Bladen 1979). The results extend and complement those of Green et. al. (1980) who showed that aprophen was as effective as atropine in the treatment of nerve agent poisoning. (Author)