Putting Theory into Practice: James Black, Receptor Theory and the Development of the Beta-Blockers at ICI, 1958–1978

Abstract

The concept of drug receptors has played a significant role in the biomedical sciences and in pharmaceutical innovation in the second half of the twentieth century. Although the concept dates back to the work of the German bacteriologist and immunologist Paul Ehrlich and of the British physiologist John Newport Langley at the end of the nineteenth and the beginning of the twentieth century, its acceptance was delayed because of conflicting ideas about drug action, and because of uncertainties and hesitations about the concept itself.

Synthesis and In Vitro Pharmacological Evaluation of 5‐(Alkoxymethyl)‐2‐(3‐alkylamino‐2‐hydroxypropoxy)phenylethanones Related to Acebutolol and Celiprolol

“…The developmental history of b-adrenoceptor blockers confirms that the pharmacological activity of these compounds is based on an essential aryloxyaminopropanol structure [11,12]. Numerous derivatives have been synthesized and the basic relationship between their chemical structure and biological activity has been established [13,14].…”

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

“…The notion of dual receptors was a neat way to explain the paradoxical effects of adrenaline and its derivatives as cardiac stimulants and bronchodilators. This prompted Black to search for drugs that preferentially blocked one receptor subtype but not the other and this eventually led to the discovery of the first effective beta‐blocker (propranolol) . This medication became widely used for the treatment of coronary heart disease (angina), hypertension, and other cardiovascular problems.…”

“…One of the actions of histamine was to promote secretion of gastric acid via the parietal cells, and this was not prevented by treatment with any of the available antihistamine drugs, which preferentially bound to H 1 ‐receptor subtypes. By direct analogy with the adrenoreceptor antagonists (beta‐blockers), James Black realized that multiple receptors for other endogenous substances existed, such as histamine …”

A binding question: the evolution of the receptor concept

“…James Black, who was the originator of both these groups of drugs, was awarded the Nobel Prize for Medicine or Physiology in 1988 [3]. By this time other researchers had elucidated the protein structure and genetic basis of various other receptors and had even visualised some of them with electron microscopy.…”