RESUMO
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.
Assuntos
Antagonistas Adrenérgicos beta/história , Descoberta de Drogas/história , Antagonistas dos Receptores H2 da Histamina/história , Farmacologia/história , Antagonistas Adrenérgicos beta/farmacologia , Cimetidina/história , Cimetidina/farmacologia , Descoberta de Drogas/métodos , Antagonistas dos Receptores H2 da Histamina/farmacologia , História do Século XX , Humanos , Farmacologia/métodos , Propranolol/história , Propranolol/farmacologia , Pesquisa/históriaAssuntos
Antagonistas Adrenérgicos beta/história , Cardiopatias/história , Antagonistas dos Receptores H2 da Histamina/história , Hepatopatias/história , Farmacologia/história , Propranolol/história , Antagonistas Adrenérgicos beta/uso terapêutico , Pesquisa Biomédica/história , Indústria Farmacêutica/história , Cardiopatias/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , História do Século XX , História do Século XXI , Humanos , Hepatopatias/tratamento farmacológico , Prêmio Nobel , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/história , Propranolol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , EscóciaRESUMO
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.
Assuntos
Gastroenterologia/história , Fármacos Gastrointestinais/história , Gastroenteropatias/história , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/história , Austrália , Gastroenterologia/tendências , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/história , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/história , História do Século XX , História do Século XXI , Humanos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/história , Inibidores da Bomba de Prótons/história , Medição de Risco , Fatores de RiscoAssuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Úlcera Péptica/microbiologia , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/história , História do Século XX , Humanos , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/história , Neoplasias Gástricas/microbiologiaAssuntos
Antiulcerosos/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Antiulcerosos/história , Infecções por Helicobacter/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/história , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , História do Século XX , Humanos , Canais de Potássio/efeitos dos fármacosRESUMO
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.
