New Research Areas

Another type of inhibitor selective for the gastric H + /K+-ATPase, as compared to the other homologous ATPases such as the Na+/K+-, Ca2 + -, and nongastric H + /K+-ATPases, are the K+ competitive inhibitors that bind to the outside face of the pump and prevent pump recycling.44 Their mechanism of action results in a more rapid and more complete inhibition of acid secretion, promising better symptom relief. Their effectiveness depends entirely on the plasma half-life, and, with a half-life of about 6 h, dosing in the morning and the evening might provide more rapid healing and almost immediate symptom relief.45 However, since their selectivity is entirely structure-dependent and does not have the acid activation benefit of the PPIs, the safety of these products (Figure 7), if introduced to the market, may be a concern.

In terms of monotherapy for H. pylori, there are some relatively obvious targets. For example, carbonic anhydrase inhibitors such as acetazolamide deserve clinical trials for eradication, especially given reports that treatment with acetazolamide resulted in a cure of PUD. Inhibition of the unique proton-gated urea channel Urel would also result in eradication, but discovery of a compound with such an action requires high-throughput screening of a chemical library. For this to occur, the pharmaceutical industry needs to recognize the importance of prevention of gastric cancer worldwide rather than just focusing on the decline of PUD in the western world.

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