[3H]Doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates

Vinh Tan Tran, Richard Lebovitz, Lawrence Toll, Solomon H. Snyder

Research output: Contribution to journalArticle


[3H]Doxepin, a tricyclic antidepressant, binds to brain homogenates with two saturable components. The high affinity component, with a dissociation constant (KD) of 0.26 nM, is associated with histamine H1-receptors. This high affinity binding shows stereospecificity in that d-chlorpheniramine is 100 times more potent than the pharmacologically less active l-isomer. Its drug specificity and regional variation closely parallel those exhibited by [3H]mepyramine binding. The drug specificity of the low affinity component is distinct from that of histamine H1-receptors, with no stereospecifityty for chlorpheniramine isomers. Furthermore, all the H1-histamine antagonists tested display micromolar potency at the low-affinity doxepin sites but nanomolar potency at the high-affinity doxepin sites associated with a physiological histamine H1-receptor. The drug specificity of the low affinity site does not correspond to that of any known neurotransmitter receptor. Tricyclic antidepressants display IC50 values of 30-600 nM for the inhibition of [3H]doxepin binding to the low-affinity component with most values in the 0.1-0.3 μM affinity range.

Original languageEnglish (US)
Pages (from-to)501-509
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number4
StatePublished - Apr 9 1981



  • Chlorpheniramine
  • Guinea pig brain
  • Histamine H-receptor
  • Mepyramine
  • Rat brain
  • Tricyclic antidepressant
  • [H]Doxepin

ASJC Scopus subject areas

  • Pharmacology

Cite this