[Impromidine-analogous guanidines: synthesis and activity at the histamine H2-receptor. 29. Histamine analogs]

Arzneimittelforschung. 1988 Mar;38(3):327-32.
[Article in German]

Abstract

19 impromidine analogous guanidines were synthetized by acid hydrolysis of the corresponding N-cyanoguanidines. The guanidines were tested on the isolated spontaneously beating guinea-pig atrium for histamine H2-receptor affinity. Lengthening the ethyl chain of cysteamine by one methylene group leads to partial agonists of decreased activity. Impromidine congeners containing a branched cimetidine side chain prove to be potent H2-agonists with maximal or near maximal response. Affinity ratios in favour of the (R)-configurated enantiomers are moderate but clearly significant. The interaction between the affinity contributing moiety and the complementary receptor area shows a lower degree of stereoselectivity than does the efficacy contributing (imidazole-4-yl)propyl substituent of impromidine and sopromidine, respectively. Homoisohistamine derivatives dramatically lose both efficacy and affinity.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Guanidines / chemical synthesis*
  • Guanidines / pharmacology
  • Guinea Pigs
  • Heart / drug effects*
  • Histamine H2 Antagonists / chemical synthesis
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Impromidine
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Myocardium / metabolism*
  • Receptors, Histamine H2 / drug effects*
  • Trachea / drug effects

Substances

  • Guanidines
  • Histamine H2 Antagonists
  • Imidazoles
  • Receptors, Histamine H2
  • Impromidine