Agents and Actions

, Volume 7, Issue 1, pp 39–43

Dimaprit, [S-[3-(N,N-dimethylamino)propyl]isothiourea]. A highly specific histamine H2-receptor agonist. Part 2. Structure-activity considerations

  • G. J. Durant
  • C. R. Ganellin
  • M. E. Parsons
Selected Papers Given at the ‘5th Annual Meeting of the European Branch of the Histamine Club’, Paris, 6–8 May 1976

DOI: 10.1007/BF01964879

Cite this article as:
Durant, G.J., Ganellin, C.R. & Parsons, M.E. Agents and Actions (1977) 7: 39. doi:10.1007/BF01964879

Abstract

Dimaprit, S-[3-(N,N-dimethylamino)propyl]isothiourea, appears to be a highly specific histamine H2-receptor agonist. Further indications of specificity are obtained from chemical considerations. Dimaprit has two basic centres (pKa values respectively 8.23 and 9.23, at 40°.) and at pH 7.4 about 5% of the molecules will be present as the monocation analogous to histamine monocation. Chemical comparison suggests that the −N+HMe2 group corresponds to the −N+H3 of histamine, and that the isothiourea group of dimaprit (which can undergo 1,3-prototropic tautomerism) may simulate the imidazole ring of histamine and function as a proton transfer agent at H2 receptors.

Simple structural analogues of dimaprit are only weakly active, indicating a high degree of chemical specificity for H2-receptor stimulation; such compounds (e.g. the lower homologue, SK & F 91487) may serve as useful chemical controls when studying the actions of dimaprit.

Copyright information

© Birkhäuser Verlag 1977

Authors and Affiliations

  • G. J. Durant
    • 1
  • C. R. Ganellin
    • 1
  • M. E. Parsons
    • 1
  1. 1.Smith Kline and French Laboratories LimitedThe Research InstituteWelwyn Garden CityEngland