PHARMACOLOGICAL PROPERTIES OF PEPSIN INHIBITORS

Abstract

SummaryA review of the literature along with certain experimental studies in our laboratories on the physical, chemical and biological properties of a variety of synthetic sulfated polysaccharides have shown that the pharmacological activities of these substances seem to depend upon a complex interaction of two or more physical or chemical parameters. For example, only fair correlations existed between high antipepsin, antiulcer and anticoagulant activity and high molecular weight or sulfate content. The roles of monosaccharide content, chain shape or the type of glucosidic linkage were difficult to evaluate with the data at hand.Sulfated amylopectin (SN‐263) with high molecular weight and sulfate content along with a branched chain shape was found to be an active pepsin inhibitor with relatively low anticoagulant activity. Pepsin inhibition studies were carried out using both the hemoglobin and the RISA methods. Oral administration of SN‐263 to pyloric‐ligated rats has shown significant inhibition of gastric ulceration with reductions in proteolytic activity of the gastric juice. The volume of gastric juice or secretion of free and total acid were not significantly altered. SN‐263 also inhibited Δ1‐cortisol‐induced gastric ulceration in rats and histamine‐induced duodenal ulcers in guinea pigs. Reserpine‐induced ulceration in the rat was not significantly affected. SN‐263 possessed low anticoagulant activity both in vitro and when given i.v. to dogs. However, no effects on blood coagulation were found after large oral doses administered to normal dogs or to rats with previously induced ulcers. SN‐263 was nonanticholinergic and did not affect gastrointestinal propulsion, as measured by the charcoal meal test in mice.