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Inflammation Research

, Volume 60, Issue 1, pp 103–110 | Cite as

Personal reflections on Sir James Black (1924–2010) and histamine

  • C. Robin Ganellin
History of inflammation

Abstract

Sir James Black, Nobel laureate (1988), became interested in the role of histamine in gastric acid secretion in the early 1950s. In 1964, he joined the pharmaceutical company Smith Kline and French Laboratories at their English subsidiary to seek a new type of antagonist that would block those actions of histamine that were not blocked by mepyramine. No such compound was known and working with medicinal chemists it took four years to discover a lead compound. Further work provided the compound burimamide, which was used to define histamine H2 receptors in 1972 for the first time, and to verify the action in human volunteers. Subsequent work led to the drug metiamide, which was withdrawn during early clinical trials. This was replaced by cimetidine, which was launched in 1977, as the first histamine H2-receptor antagonist and which revolutionized the treatment of peptic ulcer disease. The characterisation of a second type of histamine receptor revitalised interest in histamine and led to many later studies on the role of histamine in inflammation.

Keywords

Histamine Anti-histamine GI drugs 

References

  1. 1.
    Black James. Reflections on the analytical pharmacology of histamine H2-receptor antagonists. Gastroenterology. 1993;105:963–8.PubMedGoogle Scholar
  2. 2.
    Johnson LR. Control of gastric secretion: no room for histamine? Gastroenterology. 1971;61:106–18.PubMedGoogle Scholar
  3. 3.
    SmithKline and French Laboratories Ltd, the British subsidiary of the US company headquartered in Philadelphia, PA was established in Welwyn Garden City in 1960. The parent company underwent several mergers becoming, in turn, SmithKline Beckman, SmithKline Beecham and then, by 2000, GlaxoSmithKline.Google Scholar
  4. 4.
    Black James. Drugs from emasculated hormones: the principle of syntopic antagonism. Science. 1989;245:486–93.CrossRefPubMedGoogle Scholar
  5. 5.
    Ghosh MN, Schild HO. Continuous recording of acid gastric secretion in the rat. Br J Pharmacol. 1958;13:54–61.Google Scholar
  6. 6.
    Parsons ME. Quantitative studies of drug-induced acid gastric secretion in the rat. PhD Thesis, University of London; 1969.Google Scholar
  7. 7.
    Ash ASF, Schild HO. Receptors mediating some actions of histamine. Br J Pharmacol. 1966;27:427–39.Google Scholar
  8. 8.
    Durant GJ, Parsons ME, Black JW. Potential histamine H2-receptor antagonists. 2. N α-Guanylhistamine. J Med Chem. 1975;18:830–3.CrossRefPubMedGoogle Scholar
  9. 9.
    Ganellin CR, Durant GJ, Emmett JC. Some chemical aspects of histamine H2-receptor antagonists. Fed Proc. 1976;35:1924–30.PubMedGoogle Scholar
  10. 10.
    Ganellin CR. Chemistry and structure–activity relationships of H2-receptor antagonists. Hand Exp Pharmacol. 1977;18(2):251–94.Google Scholar
  11. 11.
    Parsons ME, Blakemore RC, Durant GJ, Ganellin CR, Rasmussen AC. 3-[4(5)-Imidazolyl]propylguanidine: a partial agonist at histamine H2-receptors. Agents Actions. 1975;5:464.CrossRefPubMedGoogle Scholar
  12. 12.
    Ganellin R. Medicinal chemistry and dynamic structure-activity analysis in the discovery of drugs acting at histamine H2 receptors. J Med Chem. 1981;24:913–20.CrossRefPubMedGoogle Scholar
  13. 13.
    Parsons ME, Owen DAA, Ganellin CR, Durant GJ. Dimaprit-[S-[3-(N, N-dimethylamino)propyl]isothiourea]—a highly specific histamine H2-receptor agonist. Part 1. Pharmacology. Agents Actions. 1977;7:31–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Durant GJ, Ganellin CR, Parsons ME. Dimaprit-[S-[3-(N, N-dimethylamino)propyl] isothiourea]—a highly specific histamine H2-receptor agonist. Part 2. Structure–activity considerations. Agents Actions. 1977;7:38–43.CrossRefGoogle Scholar
  15. 15.
    Black JW, Duncan WAM, Durant GJ, Ganellin CR, Parsons ME. Definition and antagonism of histamine H2-receptors. Nature. 1972;236:385–90.CrossRefPubMedGoogle Scholar
  16. 16.
    Wyllie JH, Hesselbo T, Black JW. Effects in man of histamine H2-receptor blockade by burimamide. Lancet. 1972;ii:1117–20.CrossRefGoogle Scholar
  17. 17.
    Black JW, Durant GJ, Emmett JC, Ganellin CR. Sulphur-methylene isosterism in the development of metiamide, a new histamine H2-receptor antagonist. Nature. 1974;248:65–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Wyllie JH, Ealding WDP, Hesselbo T, Black JW. Inhibition of gastric secretion in man by metiamide; a new orally active histamine H2-receptor antagonist. Gut. 1973;14:424.PubMedGoogle Scholar
  19. 19.
    Black JW, Duncan WAM, Emmett JC, Ganellin CR, Hesselbo T, Parsons ME, Wyllie JH. Metiamide—an orally active histamine H2-receptor antagonist. Agents Actions. 1973;3:133–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Treatment of duodenal ulcer by metiamide. A multicentre trial. Lancet. 1975; ii:779–81.Google Scholar
  21. 21.
    Forrest JAH, Shearman DJC, Spence R, Celestin LR. Neutropenia associated with metiamide. Lancet. 1975;i:392–3.CrossRefGoogle Scholar
  22. 22.
    Brimblecombe RW, Duncan WAM, Durant GJ, Ganellin CR, Parsons ME, Black JW. The pharmacology of cimetidine, a new histamine H2-receptor antagonist. Br J Pharmacol. 1975;53:435–6.Google Scholar
  23. 23.
    Durant GJ, Emmett JC, Ganellin CR, Miles PD, Prain HD, Parsons ME, White GR. Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine. J Med Chem. 1977;20:901–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Department of ChemistryUniversity College London, Christopher Ingold LaboratoriesLondonUK

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