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

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Cusack B, Nelson A, Richelson E

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

Psychopharmacology (Berl). 1994 May;114(4):559-65.

PubMed ID
7855217 [ View in PubMed
]
Abstract

Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for 17 antidepressants and two of their metabolites at histamine H1, muscarinic, alpha 1-adrenergic, alpha 2-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 alpha 2-adrenergic and 5-HT1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at alpha 2-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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Amitriptyline5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Inhibitor
Inducer
Details
Amitriptyline5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
AmitriptylineAlpha-1A adrenergic receptorProteinHumans
No
Antagonist
Inhibitor
Details
AmitriptylineHistamine H1 receptorProteinHumans
No
Antagonist
Details
AmitriptylineMuscarinic acetylcholine receptor (Protein Group)Protein groupHumans
Unknown
Ligand
Details
AtropineMuscarinic acetylcholine receptor M1ProteinHumans
Yes
Antagonist
Details
AtropineMuscarinic acetylcholine receptor M2ProteinHumans
Yes
Antagonist
Details
AtropineMuscarinic acetylcholine receptor M3ProteinHumans
Yes
Antagonist
Details
AtropineMuscarinic acetylcholine receptor M4ProteinHumans
Yes
Antagonist
Details
AtropineMuscarinic acetylcholine receptor M5ProteinHumans
Yes
Antagonist
Details
BrompheniramineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
ChlorprothixeneMuscarinic acetylcholine receptor M1ProteinHumans
No
Antagonist
Details
ChlorprothixeneMuscarinic acetylcholine receptor M2ProteinHumans
No
Antagonist
Details
ChlorprothixeneMuscarinic acetylcholine receptor M3ProteinHumans
No
Antagonist
Details
ChlorprothixeneMuscarinic acetylcholine receptor M4ProteinHumans
No
Antagonist
Details
ChlorprothixeneMuscarinic acetylcholine receptor M5ProteinHumans
No
Antagonist
Details
Desipramine5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Binder
Details
Desipramine5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
DesipramineAlpha-1 adrenergic receptors (Protein Group)Protein groupHumans
No
Antagonist
Details
DesipramineAlpha-2 adrenergic receptors (Protein Group)Protein groupHumans
Unknown
Binder
Details
DesipramineDopamine D2 receptorProteinHumans
Unknown
Binder
Details
DesipramineHistamine H1 receptorProteinHumans
No
Antagonist
Details
DesipramineMuscarinic acetylcholine receptor M1ProteinHumans
No
Antagonist
Details
DesipramineMuscarinic acetylcholine receptor M2ProteinHumans
No
Antagonist
Details
DesipramineMuscarinic acetylcholine receptor M3ProteinHumans
No
Antagonist
Details
DesipramineMuscarinic acetylcholine receptor M4ProteinHumans
No
Antagonist
Details
DesipramineMuscarinic acetylcholine receptor M5ProteinHumans
No
Antagonist
Details
Doxepin5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Antagonist
Details
Doxepin5-hydroxytryptamine receptor 2AProteinHumans
Unknown
Antagonist
Details
Doxepin5-hydroxytryptamine receptor 2BProteinHumans
Unknown
Antagonist
Details
Doxepin5-hydroxytryptamine receptor 2CProteinHumans
Unknown
Antagonist
Details
DoxepinAlpha-1A adrenergic receptorProteinHumans
Unknown
Antagonist
Details
DoxepinAlpha-1B adrenergic receptorProteinHumans
Unknown
Antagonist
Details
DoxepinAlpha-1D adrenergic receptorProteinHumans
Unknown
Antagonist
Details
DoxepinHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
DoxepinMuscarinic acetylcholine receptor M1ProteinHumans
Unknown
Antagonist
Details
DoxepinMuscarinic acetylcholine receptor M2ProteinHumans
Unknown
Antagonist
Details
DoxepinMuscarinic acetylcholine receptor M3ProteinHumans
Unknown
Antagonist
Details
DoxepinMuscarinic acetylcholine receptor M4ProteinHumans
Unknown
Antagonist
Details
DoxepinMuscarinic acetylcholine receptor M5ProteinHumans
Unknown
Antagonist
Details
Etoperidone5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
Etoperidone5-hydroxytryptamine receptor 2CProteinHumans
Yes
Agonist
Details
EtoperidoneAlpha-1 adrenergic receptors (Protein Group)Protein groupHumans
Unknown
Antagonist
Details
EtoperidoneAlpha-2 adrenergic receptors (Protein Group)Protein groupHumans
Unknown
Antagonist
Details
EtoperidoneDopamine D2 receptorProteinHumans
Unknown
Antagonist
Details
EtoperidoneMuscarinic acetylcholine receptor (Protein Group)Protein groupHumans
Unknown
Antagonist
Details
Imipramine5-hydroxytryptamine receptor 2AProteinHumans
Unknown
Antagonist
Details
ImipramineAlpha-1A adrenergic receptorProteinHumans
No
Antagonist
Details
ImipramineHistamine H1 receptorProteinHumans
No
Antagonist
Details
ImipramineMuscarinic acetylcholine receptor M1ProteinHumans
No
Antagonist
Details
ImipramineMuscarinic acetylcholine receptor M2ProteinHumans
No
Antagonist
Details
ImipramineMuscarinic acetylcholine receptor M3ProteinHumans
No
Antagonist
Details
ImipramineMuscarinic acetylcholine receptor M4ProteinHumans
No
Antagonist
Details
ImipramineMuscarinic acetylcholine receptor M5ProteinHumans
No
Antagonist
Details
Nefazodone5-hydroxytryptamine receptor 1AProteinHumans
Yes
Antagonist
Details
Nefazodone5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
NefazodoneAlpha-1A adrenergic receptorProteinHumans
No
Antagonist
Details
NefazodoneAlpha-2A adrenergic receptorProteinHumans
Unknown
Antagonist
Details
Nortriptyline5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Antagonist
Details
Nortriptyline5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
NortriptylineAlpha-1A adrenergic receptorProteinHumans
No
Antagonist
Details
NortriptylineHistamine H1 receptorProteinHumans
No
Antagonist
Details
NortriptylineMuscarinic acetylcholine receptor (Protein Group)Protein groupHumans
Unknown
Antagonist
Details
ParoxetineMuscarinic acetylcholine receptor (Protein Group)Protein groupHumans
Unknown
Inhibitor
Details
PimozideDopamine D2 receptorProteinHumans
Yes
Antagonist
Details
Trazodone5-hydroxytryptamine receptor 1AProteinHumans
Yes
Antagonist
Partial agonist
Details
Trazodone5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
TrazodoneAlpha-1A adrenergic receptorProteinHumans
No
Antagonist
Details
TrazodoneAlpha-2A adrenergic receptorProteinHumans
No
Antagonist
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
EtoperidoneSodium-dependent dopamine transporterProteinHumans
No
Inhibitor
Details
EtoperidoneSodium-dependent noradrenaline transporterProteinHumans
No
Inhibitor
Details
EtoperidoneSodium-dependent serotonin transporterProteinHumans
No
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Amitriptyline5-hydroxytryptamine receptor 1AKi (nM)450N/AN/ADetails
Amitriptyline5-hydroxytryptamine receptor 2CKi (nM)18N/AN/ADetails
AmitriptylineAlpha-2A adrenergic receptorKi (nM)690N/AN/ADetails
AmitriptylineHistamine H1 receptorKi (nM)0.95N/AN/ADetails
BrompheniramineHistamine H1 receptorKi (nM)6.06N/AN/ADetails
Desipramine5-hydroxytryptamine receptor 1AKi (nM)6400N/AN/ADetails
Desipramine5-hydroxytryptamine receptor 2CKi (nM)350N/AN/ADetails
DesipramineHistamine H1 receptorKi (nM)60N/AN/ADetails
DesipramineMuscarinic acetylcholine receptor M2Ki (nM)66N/AN/ADetails
Doxepin5-hydroxytryptamine receptor 1AKi (nM)276N/AN/ADetails
Doxepin5-hydroxytryptamine receptor 2CKi (nM)27N/AN/ADetails
DoxepinHistamine H1 receptorKi (nM)0.17N/AN/ADetails
DoxepinMuscarinic acetylcholine receptor M2Ki (nM)23N/AN/ADetails
Fluoxetine5-hydroxytryptamine receptor 2CKi (nM)280N/AN/ADetails
Imipramine5-hydroxytryptamine receptor 1AKi (nM)5800N/AN/ADetails
Imipramine5-hydroxytryptamine receptor 2CKi (nM)150N/AN/ADetails
ImipramineHistamine H1 receptorKi (nM)37N/AN/ADetails
ImipramineMuscarinic acetylcholine receptor M2Ki (nM)46N/AN/ADetails
Nefazodone5-hydroxytryptamine receptor 1AKi (nM)80N/AN/ADetails
Nefazodone5-hydroxytryptamine receptor 2CKi (nM)26N/AN/ADetails
NefazodoneAlpha-2A adrenergic receptorKi (nM)640N/AN/ADetails
Nortriptyline5-hydroxytryptamine receptor 1AKi (nM)294N/AN/ADetails
Nortriptyline5-hydroxytryptamine receptor 2CKi (nM)41N/AN/ADetails
NortriptylineHistamine H1 receptorKi (nM)6.3N/AN/ADetails
Trazodone5-hydroxytryptamine receptor 1AKi (nM)96N/AN/ADetails
Trazodone5-hydroxytryptamine receptor 2CKi (nM)25N/AN/ADetails
TrazodoneAlpha-2A adrenergic receptorKi (nM)320N/AN/ADetails
TrazodoneHistamine H1 receptorKi (nM)1100N/AN/ADetails
YohimbineAlpha-2A adrenergic receptorKi (nM)3.6N/AN/ADetails