ABSTRACT
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.
Subject(s)
Adrenergic beta-Antagonists/history , Drug Discovery/history , Histamine H2 Antagonists/history , Pharmacology/history , Adrenergic beta-Antagonists/pharmacology , Cimetidine/history , Cimetidine/pharmacology , Drug Discovery/methods , Histamine H2 Antagonists/pharmacology , History, 20th Century , Humans , Pharmacology/methods , Propranolol/history , Propranolol/pharmacology , Research/historySubject(s)
Adrenergic beta-Antagonists/history , Heart Diseases/history , Histamine H2 Antagonists/history , Liver Diseases/history , Pharmacology/history , Propranolol/history , Adrenergic beta-Antagonists/therapeutic use , Biomedical Research/history , Drug Industry/history , Heart Diseases/drug therapy , Histamine H2 Antagonists/therapeutic use , History, 20th Century , History, 21st Century , Humans , Liver Diseases/drug therapy , Nobel Prize , Peptic Ulcer/drug therapy , Peptic Ulcer/history , Propranolol/therapeutic use , Randomized Controlled Trials as Topic , ScotlandABSTRACT
There have been numerous and dramatic advances in our understanding of the mechanisms, causes and treatments of upper gastrointestinal diseases in the past 50 years. This review focuses on a few, not dealt with elsewhere in this special issue of the Journal. The early history of the recognition that nonsteroidal anti-inflammatory drugs are a major cause of peptic ulcer is described, with particular attention to the work of the pioneering Australian investigators. The story of the development of the histamine H(2)-receptor antagonists and the proton pump inhibitors is also outlined.
Subject(s)
Gastroenterology/history , Gastrointestinal Agents/history , Gastrointestinal Diseases/history , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/history , Australia , Gastroenterology/trends , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/history , Gastrointestinal Agents/therapeutic use , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/drug therapy , Histamine H2 Antagonists/history , History, 20th Century , History, 21st Century , Humans , Peptic Ulcer/chemically induced , Peptic Ulcer/history , Proton Pump Inhibitors/history , Risk Assessment , Risk FactorsSubject(s)
Helicobacter Infections/complications , Helicobacter pylori , Peptic Ulcer/microbiology , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Histamine H2 Antagonists/history , History, 20th Century , Humans , Peptic Ulcer/drug therapy , Peptic Ulcer/history , Stomach Neoplasms/microbiologyABSTRACT
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.