Novel Diuretic and Inhibitor of Gastric Acid Secretion

Abstract:
Excess secretion of gastric acid gives rise to a number of pathological disorders such as ulcers, gastritis, gastroesophageal reflux disease, Zollinger-Ellison syndrome (ZES), etc. ZES and peptic ulcers in particular are widespread diseases that can have serious complications. Histamine H2-antagonists have been successfully used as acid output (AO) inhibiting agents, but their erratic and diminishing responses and their tendency to produce progressively more severe side effects has led some researchers to explore the use of proton pump inhibitors (PPIs) as an alternative. PPIs directly block the final step of proton production in the parietal cells, but practical therapeutic applications of such compounds as AO inhibitors has so far been held back by their relatively low efficacy.

To achieve higher PPI efficacy and thus more reasonable dose levels for treating gastric acid disorders, Researchers have identified a compound (currently used as a clinical diagnostic agent) that, when co-administered with a PPI, greatly increases the PPI's efficacy. Thus, formulations of the compound or its analogs together with a PPI yield a greater duration and/or intensity of acid attenuation than is the case for the PPI alone, making such formulations highly attractive as candidate pharmaceuticals.

The Researchers also discovered that the same compound (without the PPI) also increases urinary sodium excretion. Thus, it has further potential pharmaceutical application as a diuretic agent for treating pathological disorders involving excess fluid retention, notably high blood pressure, heart failure, kidney failure/renal dysfunction, calcium kidney stones, and cirrhosis.