Personal reflections on Sir James Black (1924–2010) and histamine

Abstract

Sir James Black, Nobel laureate (1988), became interested in the role of histamine in gastric acid secretion in the early 1950s. In 1964, he joined the pharmaceutical company Smith Kline and French Laboratories at their English subsidiary to seek a new type of antagonist that would block those actions of histamine that were not blocked by mepyramine. No such compound was known and working with medicinal chemists it took four years to discover a lead compound. Further work provided the compound burimamide, which was used to define histamine H(2) receptors in 1972 for the first time, and to verify the action in human volunteers. Subsequent work led to the drug metiamide, which was withdrawn during early clinical trials. This was replaced by cimetidine, which was launched in 1977, as the first histamine H(2)-receptor antagonist and which revolutionized the treatment of peptic ulcer disease. The characterisation of a second type of histamine receptor revitalised interest in histamine and led to many later studies on the role of histamine in inflammation.

Histamine Receptors and Antihistamines: From Discovery to Clinical Applications

“…This approach led to the identification of burimamide that blocked histamine effects on both the beating guinea pig atrium and the rat gastric acid secretion [29] . These findings, communicated in a classical paper in Nature in 1972 [29] , provided the first pharmacological demonstration of H 2 R distinct from H 1 R. After burimamide, several other H 2 R antagonists were developed that revolutionized the treatment of peptic ulcer [28,30,31] .…”

“…The discovery of histamine H 2 R is linked to the name of the Nobel Laureate Sir James Black [28] . He hypothesized that anti-H 2 drugs should be more similar to histamine because anti-H 1 compounds were significantly different to histamine.…”

Perspectives in Drug Development and Clinical Pharmacology: The Discovery of Histamine H1 and H2 Antagonists

“…The principal scientists involved in this drug discovery were awarded the Noble Prize in Physiology or Medicine for their efforts (Figure ) . These pioneers were credited with discovering histamine's biological activity (Henry Dale), the synthesis and testing of drugs that blocked histamine at H 1 receptors (Daniel Bovet), and the first H 2 receptor antagonist (cimetidine), which revolutionized treatment of gastric ulcers (James Black) …”

“…By tradition, the word antihistamine refers to drugs that antagonize or compete with histamine for binding to H 1 receptors, whereas these same drugs are ineffective in preventing, for example, histamine‐induced secretion of gastric acid, the commonest cause of peptic ulcers . The driving force behind the discovery of drugs that blocked histamine‐induced secretion of gastric acid was a Scottish physician, Sir James Black (1924–2010) . The deliberating condition of peptic ulcers causes intense pain, especially at mealtimes and during the night.…”

“…33 The driving force behind the discovery of drugs that blocked histamine-induced secretion of gastric acid was a Scottish physician, Sir James Black (1924Black ( -2010. 34 The deliberating condition of peptic ulcers causes intense pain, especially at mealtimes and during the night. If untreated, the condition could become life threatening owing to perforated ulcers and intragastric bleeding.…”