James W. Black (1924–2010)
Histamine attracted considerable scientific attention during the early decades of the twentieth century as a naturally occurring, highly active chemical. As the years progressed, a link was found between the release of histamine and allergic reactions; and in 1944, Neo-Antergan—the first antihistamine—appeared, followed by dozens of similar drugs.
To a greater or lesser extent, all these successors were comparable in treating allergic disorders, but none of them could block histamine’s ability to stimulate gastric-acid release in the stomach—a cause of peptic ulcers. Scottish physician-pharmacologist James Black speculated that multiple histamine receptor types—one involved with the allergic response, another with acid secretion, for example—might underlie this anomaly. Thus, Black, then working at the Smith, Kline and French Research Institute in Hertfordshire, England, set out to develop a drug that could antagonize histamine’s second receptor type.
In 1976, after twelve years of effort, Tagamet (cimetidine) was brought to market. The first member of a new class of drugs that rendered all previous ulcer and gastroesophageal reflux disease (GERD or heartburn) drugs obsolete, Tagamet not only reduced acid release but also promoted healing of gastric ulcers. With Tagamet’s discovery, the designation antihistamine was now ambiguous and required additional specification. The classical antihistamines used to treat allergies were redesignated histamine H1 receptor antagonists, while Tagamet-like drugs were classified as H2 antagonists.
ONE SCIENTIST, TWO REVOLUTIONARY DRUGS. Tagamet became the world’s best-selling drug in 1981, with annual sales exceeding $1 billion and displacing the heart drug Inderal (propranolol), another Black-developed medicine in the top spot. Tagamet, in turn, was displaced and relegated to the second slot in 1988 by Zantac (ranitidine), another H2 antagonist with fewer side effects. In recognition for his discoveries of Inderal and Tagamet, two revolutionary drugs, Black was named a co-recipient of the 1988 Nobel Prize in Physiology or Medicine.
SEE ALSO Drug Receptors (1905), Neo-Antergan (1944), Benadryl (1946), Propranolol (1964), Prilosec (1989).
Antihistamines are of two distinct types: those that treat allergic disorders (Neo-Antergan, Benadryl) and those that prevent the secretion of acid in the stomach. Tagamet was the first of the acid-inhibiting drugs, effectively combating heartburn (commonly caused by the consumption or overconsumption of spicy chilies, carbonated drinks, and various acid reflux–promoting food and beverages) as well as ulcers.