Histamine H1 receptors in human brain labelled with [3H]doxepin.
Article Details
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Kanba S, Richelson E
Histamine H1 receptors in human brain labelled with [3H]doxepin.
Brain Res. 1984 Jun 18;304(1):1-7.
- PubMed ID
- 6146381 [ View in PubMed]
- 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 X 10(-10) M 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 X 10(-10) M and 7.9 +/- 0.5 X 10(-10) M, respectively. Mequitazine, a new antihistamine with a weak sedative effect, had a KD of 5.8 +/- 0.8 X 10(-9), making it ten times as potent as the classic antihistamine diphenhydramine. 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Maprotiline Histamine H1 receptor Protein Humans NoAntagonistDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Amitriptyline Histamine H1 receptor Ki (nM) 0.67 N/A N/A Details Chlorpheniramine Histamine H1 receptor Ki (nM) 30 N/A N/A Details Chlorpromazine Histamine H1 receptor Ki (nM) 3 N/A N/A Details Clozapine Histamine H1 receptor Ki (nM) 1.2 N/A N/A Details Desipramine Histamine H1 receptor Ki (nM) 120 N/A N/A Details Diphenhydramine Histamine H1 receptor Ki (nM) 62 N/A N/A Details Doxepin Histamine H1 receptor Ki (nM) 0.49 N/A N/A Details Imipramine Histamine H1 receptor Ki (nM) 16 N/A N/A Details Maprotiline Histamine H1 receptor Ki (nM) 0.79 N/A N/A Details Mepyramine Histamine H1 receptor Ki (nM) 4 N/A N/A Details Mequitazine Histamine H1 receptor Ki (nM) 5.8 N/A N/A Details Mianserin Histamine H1 receptor Ki (nM) 0.36 N/A N/A Details Nortriptyline Histamine H1 receptor Ki (nM) 8.4 N/A N/A Details Trimipramine Histamine H1 receptor Ki (nM) 1.4 N/A N/A Details