Gastric acid discovery

The discovery of the first nonpetide CCK antagonist, the natural product asperlicin, in 1985 (495) shifted the medicinal chemistry focus from peptides to small molecule antagonists (496,497).CCK-B receptors are the dominant isoform in the brain, and antagonists at this subtype are potential anxiolytics. Many CCK-B antagonists also modulate gastric acid secretion through peripheral CCK-B (gastrin) receptors. 

The aim of this review is to outline the drugs that are currently available and the medicinal chemistry that led to their discovery. The physiological processes associated with acid secretion and the mechanism of action of inhibitors of this process are described. Current research into inhibitors of gastric acid secretion is aimed at producing a reversible PPI or antagonist of receptor-mediated acid secretion. The medicinal chemistry and pharmacology of such approaches are considered. 

Table 3.2 Time-Related Discoveries with Respect to Gastric Acid Secretion...

The concept that the stomach secreted acid and digestive enzymes was not fully appreciated until the nineteenth century, although various hypotheses had been mooted since the time of the ancient Greeks. The discovery of gastric acid (7) was the first step to under-... 

Roberts S, McDonald IM. Inhibitors of gastric acid secretion. In Abraham DJ, ed. Burger s Medicinal Chemistry and Drug Discovery, vol 4. Autocoids, Diagnostics, and Drugs from New Biology. 6th Ed. Hoboken, NJ Wiley-Interscience, 2003 85-127. 

Section 1 The Production of Acid in the Stomach Chapter 1 The Discovery of Acid Chapter 2 The Discovery of Ion Pumps Chapter 3 Ion-Motive Adenosine Triphosphatases Chapter 4 The Gastric Acid Pump... 

The discovery and increasing understanding of the importance of the H, K -ATPase in the late 1970s revolutionized our knowledge of the physiology of gastric acid secretion [25]. It is well accepted that the activation of H, K -ATPase is the final step in the stimulation of acid secretion and the specific PPIs, the substituted benzimidazoles, completely inhibit gastric acid secretion stimulated by cAMP and histamine [2]. 

It is only the ability of modern chemistry to detect very small quantities of materials that made the following discovery possible. In some recent research it was reported that one subtle way in which cancer tumours cells differ from normal cells is how they metabolize carbohydrates present on their surfaces. Cancer cells have far more of the carbohydrate sialic acid, which can be detected with MRI (magnetic resonance imaging) analytical techniques. It was found that the sialic acid normally appears on the surface of the cells only in foetal development, but it appears abnormally in patients with gastric, colon, pancreatic, liver, lung, prostate and breast cancers, as well as in leukaemia. Research is continuing.1... 

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