Elsevier

Brain Research

Volume 304, Issue 1, 18 June 1984, Pages 1-7
Brain Research

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

https://doi.org/10.1016/0006-8993(84)90856-4Get rights and content

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.)of3.1 ± 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, withKDs of3.6 ± 0.7 × 10−10M and7.9 ± 0.5 × 10−10M, respectively. Mequitazine, a new antihistamine with a weak sedative effect, had aKDof5.8 ± 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.

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