A new era of logical drug design


The research program leading to cimetidine also represented a revolution in the way pharmaceuticals are developed. Traditionally, the development of a new drug would often depend on the fortuitous discovery of a plant or microbial extract that showed some of the required biological activity. Using that first extract as a lead, many similar compounds would be made and tested for pharmacological effectiveness. In many cases, the researchers did not know how the drug worked, so finding an optimal compound was difficult.

The development of cimetidine was radically different: it was one of the first drugs to be designed logically from first principles. SK&F's multidisciplinary research team first looked at the physiological cause of acid secretion. They confirmed that a molecule found in the body called histamine triggers the release of acid when it binds to a specific receptor (now called the H2-receptor) in the stomach lining. Their aim was to find a molecule that successfully competed with histamine in combining with the receptor, but then blocked, rather than stimulated, acid release. Such a molecule was called a histamine H2-receptor antagonist and represented a new class of drugs.

Using a step by step analysis of structural and physical properties, the team made a series of histamine-based molecules, which were then tested for antagonist activity using carefully designed pharmacological assays. Today, this approach of rational drug design underpins the discovery programs of many major pharmaceutical companies.

 

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A new era of logical drug design | Discovery of H2-receptor antagonists | A new receptor
Success at last | A better manufacturing process | The people | Landmark designation and acknowledgments

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