Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum

Eur J Pharmacol. 1979 Oct 15;58(4):479-83. doi: 10.1016/0014-2999(79)90320-0.


Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Female
  • Guinea Pigs
  • Histamine / pharmacology
  • Histamine H1 Antagonists*
  • Ileum / drug effects
  • In Vitro Techniques
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*


  • Antidepressive Agents, Tricyclic
  • Histamine H1 Antagonists
  • Histamine