High affinity binding of tricyclic antidepressants to histamine H1-receptors

Fact and artifact

J. E. Taylor, E. Richelson

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Six tricyclic antidepressants were tested for their ability to inhibit the binding of the histamine H1-receptor antagonist [3H]pyrilamine to membrane fractions from whole rat brain. Calculated inhibition constants (K(i)) for the antidepressants were in the range of 2.6 x 1--11 to 2.3 x 10-7 M and correlated very well with their equilibrium dissociation constants derived from biological assays of the H1-receptor. Increasing the concentration of receptors present in the binding assay resulted in an overestimation of the calculated K(i)'s for doxepin, amitriptyline, and nortriptyline, but not for the lower affinity compounds of the series, imipramine, protriptyline, and desipramine. These results indicate: (1) the importance of receptor concentration in determining the potency of compounds which competitively inhibit, with very high affinity, the binding of a radioactively labeled ligand; (2) the need to correlate binding data with biological data.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalEuropean Journal of Pharmacology
Volume67
Issue number1
DOIs
StatePublished - 1980

Fingerprint

Protriptyline
Doxepin
Histamine H1 Antagonists
Nortriptyline
Pyrilamine
Histamine H1 Receptors
Desipramine
Amitriptyline
Imipramine
Tricyclic Antidepressive Agents
Biological Assay
Artifacts
Antidepressive Agents
Ligands
Membranes
Brain

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

High affinity binding of tricyclic antidepressants to histamine H1-receptors : Fact and artifact. / Taylor, J. E.; Richelson, E.

In: European Journal of Pharmacology, Vol. 67, No. 1, 1980, p. 41-46.

Research output: Contribution to journalArticle

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