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

Article Details


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

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
DrugTargetKindOrganismPharmacological ActionActions
MaprotilineHistamine H1 receptorProteinHumans
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AmitriptylineHistamine H1 receptorKi (nM)0.67N/AN/ADetails
ChlorpheniramineHistamine H1 receptorKi (nM)30N/AN/ADetails
ChlorpromazineHistamine H1 receptorKi (nM)3N/AN/ADetails
ClozapineHistamine H1 receptorKi (nM)1.2N/AN/ADetails
DesipramineHistamine H1 receptorKi (nM)120N/AN/ADetails
DiphenhydramineHistamine H1 receptorKi (nM)62N/AN/ADetails
DoxepinHistamine H1 receptorKi (nM)0.49N/AN/ADetails
ImipramineHistamine H1 receptorKi (nM)16N/AN/ADetails
MaprotilineHistamine H1 receptorKi (nM)0.79N/AN/ADetails
MepyramineHistamine H1 receptorKi (nM)4N/AN/ADetails
MequitazineHistamine H1 receptorKi (nM)5.8N/AN/ADetails
MianserinHistamine H1 receptorKi (nM)0.36N/AN/ADetails
NortriptylineHistamine H1 receptorKi (nM)8.4N/AN/ADetails
TrimipramineHistamine H1 receptorKi (nM)1.4N/AN/ADetails