Histamine H1 receptors in human brain labelled with [3H]Doxepin

Shigenobu Kanba, Elliott Richelson

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Doxepin, a tricyclic antidepressant, is one of the most potent histamine H1 antagonists. Therefore, the binding of [3H]doxepin to human brain membranes was examined. Scatchard analysis revealed two distinct binding sites. The high-affinity binding site with a dissociation constant (KD ± S.E.M.) of 3.1 ± 0.3 × 10-10M was pharmacologically identified as histamine H1 receptors. Dissociation curves at low concentrations of [3H]doxepin were biphasic, suggesting several possibilities about the interaction between [3H]doxepin and histamine H1 receptors. Tetracyclic antidepressants, mianserin and maprotiline, were very potent, with KDs of 3.6 ± 0.7 × 10-10M and 7.9 ± 0.5 × 10-10M, respectively. Mequitazine, a new antihistamine with a weak sedative effect, had a KD of 5.8 ± 0.8 × 10-9, making it ten times as potent as the classic antihistamine diphenyhydramine. The highest binding of [3H]doxepin to histamine H1 receptors was found in cerebral neocortex and the limbic system. The distribution of histamine H1 receptors in human central nervous system did not correlate with the previously reported distributions in rat brain and guinea pig brain determined by [3H]doxepin binding.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBrain Research
Volume304
Issue number1
DOIs
StatePublished - Jun 18 1984

Keywords

  • antihistamines
  • histamine H receptors
  • human brain
  • mequitazine
  • mianserin
  • tricyclic antidepressants
  • [H]doxepin

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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