The major impacts of James Black's drug discoveries on medicine and pharmacology.

James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions.

Robin Ganellin gives his views on medicinal chemistry and drug discovery. Interview by Stephen L. Carney.

Robin Ganellin was born in East London and studied chemistry at Queen Mary College, London, receiving a PhD in 1958 under Professor Michael Dewar for his research on tropylium chemistry. He joined Smith Kline & French Laboratories (SK&F) in the UK in 1958 and was one of the co-inventors of the revolutionary drug cimetidine (Tagamet(R)) He subsequently became Vice-President for Research at the company's Welwyn facility. In 1986 he was awarded a DSc from London University for his work on the medicinal chemistry of drugs acting at histamine receptors and was also made a Fellow of the Royal Society and appointed to the SK&F Chair of Medicinal Chemistry at University College London, where he is now Emeritus Professor of Medicinal Chemistry. Professor Ganellin has been honoured extensively, including such awards as the Royal Society of Chemistry Award for Medicinal Chemistry, their Tilden Medal and Lectureship and their Adrien Albert Medal and Lectureship, Le Prix Charles Mentzer de France, the ACS Division of Medicinal Chemistry Award, the Society of Chemical Industry Messel Medal and the Society for Drug Research Award for Drug Discovery. He is a past Chairman of the Society for Drug Research, was President of the Medicinal Chemistry Section of IUPAC, and is currently Chairman of the IUPAC Subcommittee on Medicinal Chemistry and Drug Development.

The development of cimetidine: 1964-1976. A human story.

There was still controversy regarding the physiology of acid secretion in 1964 when a team at Smith Kline & French Laboratories in England started a project to prove the existence of more than one receptor for histamine and to find a substance capable of blocking the effects not blocked by the commonly used antihistamines. The team was convinced that histamine was the final mediator of acid secretion. After 8 years, James Black and his coworkers published evidence of the first histamine2-receptor antagonist, burimamide. As this substance was not suitable for oral therapy, the research continued. Metiamide was synthesized with promising clinical effects but questionable safety. The final answer was cimetidine (Tagamet), approved in England in November 1976. Cimetidine was a breakthrough in the treatment of peptic ulcers. In this article I focus on the human factors lying behind many of the decisions made during the years of research. Without personal courage under stressful conditions, the H2-receptor antagonists might never have reached the market.