 |
|
Discovery of H2-receptor antagonists
The discovery of histamine H2-antagonists is a story of single-minded commitment by a group of
creative scientists working in close collaboration in the United Kingdom. The process of research and
development for economical production of the resulting drug, cimetidine, was the work of equally
creative scientists working in the United States. In 1963 George Paget, a pathologist from ICI, joined Smith Kline & French to head its R&D laboratories
at Welwyn Garden City in the United Kingdom. He soon recruited two colleagues: James Black as head of
pharmacology and William Duncan as head of biochemistry. Black had been instrumental in developing beta-blocker drugs for the treatment of heart disease. They
were based on his notion of blocking the stimulating action of a molecule (agonist) at a receptor site
implicated in the disease with a similar but inactive chemical (antagonist). He was keen to start a new
research program looking at histamine receptors and antagonists. Histamine is found throughout body tissues and is released during allergic reactions such as hay fever.
It also stimulates acid secretion in the stomach and increases the heart rate. However, tests with
antihistamines had indicated there were possibly two types of histamine (H) receptor, one of which did not
respond to antihistamines. Black wanted to establish the existence of the latter receptor and to find
histamine antagonists that selectively inhibited acid secretion. Since this work promised to lead to an
effective anti-ulcer medicine, the company started an acid secretion program in 1964. Chemists Graham Durant, Robin Ganellin, and John Emmett joined Black on the project together with Mike
Parsons, a pharmacologist. Their aim was to make chemical variants of histamine and test them for antagonism
using a combination of in vitro and in vivo assays.
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
Copyright
©2004 American Chemical Society. All Rights Reserved. 1155 16th Street
NW, Washington DC 20036
202-872-4600, 800-227-5558
