Binding of antidepressants to human brain receptors: focus on newer generation compounds

Bernadette Cusack, Albert Nelson, Elliott Richelson

Research output: Contribution to journalArticlepeer-review

292 Scopus citations


Using radioligand binding assays and postmortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for 17 antidepressants and two of their metabolites at histamine H1, muscarinic, α1-adrenergic, α2-adrenergic, dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2 receptors. Several newer antidepressants were compared with older drugs. In addition, we studied some antimuscarinic, antiparkinson, antihistamine, and neuroleptic compounds at some of these receptors. For the antidepressants, classical tricyclic antidepressants were the most potent drugs at five of the seven receptors (all but α2-adrenergic and 5-HT1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at α2-adrenergic and 5-HT1A receptors. Of ten antihistamines tested, none was more potent than doxepin at histamine H1 receptors. At muscarinic receptors antidepressants and antihistamines had a range of potencies, which were mostly weaker than those for antimuscarinics. From the in vitro data, we expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and venlafaxine not to block any of these five receptors in vivo. An antidepressant's potency for blocking a specific receptor is predictive of certain side effects and drug-drug interactions. These studies can provide guidelines for the clinician in the choice of antidepressant.

Original languageEnglish (US)
Pages (from-to)559-565
Number of pages7
Issue number4
StatePublished - May 1994


  • Antihistamines
  • Antimuscarinics
  • Dopamine D receptor
  • Histamine H receptor
  • Muscarinic receptor
  • Neuroleptics
  • Serotonin 5-HT receptor
  • Serotonin 5-HT receptor
  • α-adrenoceptor, α-adrenoceptor

ASJC Scopus subject areas

  • Pharmacology


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