Cimetidine discovery

The discovery and development of cimetidine and ranitidine provided a revolution in the medical treatment and management of peptic ulcer disease. Subsequently, many pharmaceutical companies became involved in research programs to discover additional compounds as H2-receptor histamine antagonists. As a result, a very wide range of chemical structures now exists for this class of drug (for a review, see Cooper et al. [19]). Many of these compounds have been investigated in human studies, but only the above-mentioned five drugs - cimetidine, ranitidine, nizatidine, famotidine, and roxatidine - are marketed as medicines. 

Cimetidine therapy led to a revolution in the treatment of acid-peptic disorders, with oral therapy being able to reduce the necessity of surgical procedures. The discovery of this landmark molecule caused a number of pharmaceutical companies to be alerted to this therapeutic area and target the discovery of a "better" Hz-receptor antagonist. Ranitidine was introduced by Glaxo in 1981 as a more... 

Antagonists - Recent structure-activity studies of Hj -receptor antihistamines have been concerned with stereochemical aspects, partition characteristics, pattern recognition, affinity contributions to activity and association phenomena. The subject has also been reviewed recently. Undoubtedly, the main focus of attention has been on the H2 receptor histamine antagonists. Three compounds have been widely studied, viz. burimamide (13b), metiamide (13c) and cimetidine (13d), and their pharmacological properties summarized. 3 Their discovery and development at SK F was the culmination of a research programme initiated in 1964. The search for an antagonist and some of the medicinal chemical approaches used in the structure-activity analysis have been outlined in several articles. Concurrently, other researchers had sought... 

SOURCES CJR. Ganellin, Cimetidine, Chronicles of Drug Discovery, J.S. Bindra and D. Ledniger (eds.) (New York. NY Wiley, 1982). SmithKline French International, The Discovery of Histamine H2-Receptors and Their Antagonists (Philadelphia, PA SmithKline Flench, 1982). 

Ganellin, C.R. (1982) Cimetidine. Chronicles of Drug Discovery, pp. 1-38. John Wiley and Sons, New York. 

Ganellin, C.R. (1993) Discovery of cimetidine, ranitidine and other H2-receptor histamine antagonists. Medicinal Chemistry—The Role of Organic Chemistry in Drug Research, pp. 227-255. Academic Press, London. 

There is more about the discovery of cimetidine in W. Sneader, Drug Discovery a History, Wiiey, Chichester, 2005. 

The development of the first beta-blockers by ICl was essentially based on the scientific work of the Scottish pharmacologist Sir James Black (1924-2010). For his "discoveries of important principles for drug treatment" i.e. propranolol and cimetidine, he was awarded the 1988 Nobel Prize for Physiology or Medicine. 

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