The binding of doxepin to histamine H1-receptors in guinea-pig and rat brain

Br J Pharmacol. 1985 Feb;84(2):417-24. doi: 10.1111/j.1476-5381.1985.tb12925.x.


The affinity constant for doxepin obtained from inhibition of histamine-induced contraction of guinea-pig intestinal smooth muscle at 30 degrees C was 2.6 +/- 0.18 X 10(10)M-1. The slope of a Schild plot was not significantly different from unity. The affinity constant of doxepin did not vary markedly with temperature. At 37 degrees C it was 3.75 +/- 0.02 X 10(10)M-1 and at 25 degrees C 2.1 X 10(10)M-1. Doxepin was a competitive inhibitor of [3H]-mepyramine binding to guinea-pig cerebellar homogenates. The affinity constant derived for doxepin at 30 degrees C was 1.12 +/- 0.45 X 10(10)M-1. Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-mepyramine binding in guinea-pig cerebellum, cerebral cortex and hippocampus did not differ significantly from unity. The mean affinity of mepyramine for histamine H1-receptors in rat brain homogenates at 30 degrees C was 3.5 X 10(8)M-1. Hill coefficients for curves of doxepin or mepyramine inhibition of [3H]-mepyramine binding to homogenates of rat cerebral cortex or rat whole brain were near unity. These studies provide no evidence that doxepin binds preferentially to a sub-class of histamine H1-receptors in rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / metabolism*
  • Cerebral Cortex / metabolism
  • Doxepin / metabolism*
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Intestines / drug effects
  • Kinetics
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Pyrilamine / metabolism
  • Pyrilamine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H1 / metabolism*


  • Receptors, Histamine
  • Receptors, Histamine H1
  • Doxepin
  • Pyrilamine