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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Brimblecombe, R.W. et al.

Characterization and development of cimetidine as a histamine H2-receptor antagonist.

The concept of two classes of histamine receptor, H1 and H2, is introduced and the chemical derivation of histamine H2-receptor antagonists is outlined briefly. Starting from the structure of histamine, chemical modification led eventually to burimamide, the first described histamine H2-receptor antagonist. Further stepwise modifications ultimately afforded metiamide and cimetidine. In vitro studies show that cimetidine is a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in rats and dogs after both intravenous and oral administration. It is equally potent as an inhibitor of pentagastrin-stimulated secretion. The evidence suggests that cimetidine inhibits gastric acid secretion through blockade of histamine H2-receptors in the gastric mucosa. Cimetidine has been shown to have low acute toxicity. Repeated dose studies of up to 24 months in rats and up to 12 months in dogs have been carried out and the results are presented and discussed. There is no known toxic effect which would limit the usefulness of cimetidine in man.[1]

References

Characterization and development of cimetidine as a histamine H2-receptor antagonist. Brimblecombe, R.W., Duncan, W.A., Durant, G.J., Emmett, J.C., Ganellin, C.R., Leslie, G.B., Parsons, M.E. Gastroenterology (1978) [Pubmed]

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