Proton pump inhibitors discovery

Sjostrand SE, Olbe L, Fellenius E. The discovery and development of the proton pump inhibitor. In Proton Pump Inhibitors. Olbe L. (Ed.), Birkhauser, Switzerland, 1999. 

Herling AW, Weidmann K (1996) Gastric proton pump inhibitors. In Wolff ME (ed) Burger s Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume 2 Therapeutic Agents 1996. John Wiley and Sons, New York, pp 119-151... 

H. pylori is a major etiological factor in gastroduodenal disorders such as chronic gastritis, peptic ulcer, and gastric cancer. Therefore, the treatment and prevention of these diseases would be facilitated by its eradication. At present, triple therapies that comprise two antibiotics (clarithromycin and amphotericin B) and a proton pump inhibitor are used to eradicate H. pylori. However, strains that are resistant to antibiotics have appeared. In addition, antibiotic treatment is associated with serious side effects such as nausea, vomiting, and diarrhea. Therefore, the discovery of novel antibacterial agents that are highly effective and safe is badly needed for the treatment of H. pylori infection. 

Interestingly, some histamine Hj-receptorantagonists, like ranitidine or nizatidine, in spite of their different pharmacological profile, showa certain structural relationship to nitenpyram (Fig. 8.48). Prior to the discovery of proton-pump inhibitors, these were the most important drugs for the treatment of stomach ulcers. 

The discovery and development of the proton pump inhibitor Isolated gastric glands from the rabbit... 

In 1960-1970S, a number of pharmaceutical and biotech companies worked on the discovery of inhibitors of the proton pump for the treatment of acid hypersecretion. Timoprazole was first identified by Astra Haessle (now part of AstraZeneca) as a potent PPI (Figure 8.9) [70a], which showed... 

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