Drugs from emasculated hormones: the principle of syntopic antagonism.
This lecture illustrates the early stages in the planning and discovery of propranolol, an adrenaline beta-adrenergic receptor antagonist, and cimetidine, a histamine H2-receptor antagonist--the first examples of clinically useful drugs from each of these classes. The significance of selective agonists, partial agonists, and syntopic antagonists and the importance of the bioassay and the use of molar models in the drug discovery process are discussed. For the future, an outline of potential developments in hormone-receptor concepts is offered leading to the conclusion that progress may depend on improvements in bioassays and related molar modeling.
Black
J
J
Department of Analytical Pharmacology, Rayne Institute, King's College Hospital School of Medicine and Dentistry, London, United Kingdom.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001681:Biological Assay; D004381:Duodenal Ulcer / Q000188:drug therapy; D004837:Epinephrine / Q000031:analogs & derivatives; D006632:Histamine / Q000031:analogs & derivatives; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D013276:Stomach Ulcer / Q000188:drug therapy
D000319:Adrenergic beta-Antagonists; D006635:Histamine H2 Antagonists; D006632:Histamine; D004837:Epinephrine