Black J
Department of Analytical Pharmacology, Rayne Institute, King's College Hospital School of Medicine and Dentistry, London, United Kingdom.
Science. 1989 Aug 4;245(4917):486-93. doi: 10.1126/science.2569237.
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.
本次讲座阐述了普萘洛尔（一种肾上腺素β-肾上腺素能受体拮抗剂）和西咪替丁（一种组胺H2受体拮抗剂）的研发早期阶段，它们分别是这两类临床上有用药物的首个实例。讲座还讨论了选择性激动剂、部分激动剂和同位点拮抗剂的重要性，以及生物测定法和摩尔模型在药物研发过程中的应用。展望未来，本文给出了激素受体概念潜在发展的概述，得出的结论是进展可能取决于生物测定法及相关摩尔模型的改进。
