Pharmacological profile of antidepressants and related compounds at human monoamine transporters.

Article Details

Citation

Tatsumi M, Groshan K, Blakely RD, Richelson E

Pharmacological profile of antidepressants and related compounds at human monoamine transporters.

Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58.

PubMed ID
9537821 [ View in PubMed
]
Abstract

Using radioligand binding assays, we determined the equilibrium dissociation constants (KD's) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with KD's of 0.45 +/- 0.03 nM and 8.1 +/- 0.4 nM, respectively. Sertraline (KD = 25 +/- 2 nM) and nomifensine (56 +/- 3 nM) were the two most potent antidepressants at the human dopamine transporter. We showed significant correlations for antidepressant affinities at binding to serotonin (R = 0.93), norepinephrine (R = 0.97), and dopamine (R = 0.87) transporters in comparison to their respective values for inhibiting uptake of monoamines into rat brain synaptosomes. These data are useful in predicting some possible adverse effects and drug-drug interactions of antidepressants and related compounds.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AmitriptylineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
AmitriptylineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
AmoxapineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
AmoxapineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
AtomoxetineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
AtomoxetineSodium-dependent serotonin transporterProteinHumans
Unknown
Binder
Details
BupropionSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
Butriptyline5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
ButriptylineHistamine H1 receptorProteinHumans
Yes
Antagonist
Details
ButriptylineSodium-dependent serotonin transporterProteinHumans
Yes
Antagonist
Inhibitor
Details
ChlorpheniramineSodium-dependent dopamine transporterProteinHumans
Unknown
Inhibitor
Details
ChlorpheniramineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
ChlorpheniramineSodium-dependent serotonin transporterProteinHumans
Unknown
Inhibitor
Details
ClomipramineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
ClomipramineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
CocaineSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
CocaineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
DesipramineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
DesipramineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
DexmethylphenidateSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
DexmethylphenidateSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
DoxepinSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
DoxepinSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
FluoxetineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
ImipramineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
MazindolSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
MazindolSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
MazindolSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
MethylphenidateSodium-dependent dopamine transporterProteinHumans
Yes
Inhibitor
Details
MethylphenidateSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
MianserinSodium-dependent dopamine transporterProteinHumans
Unknown
Binder
Details
MianserinSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
MianserinSodium-dependent serotonin transporterProteinHumans
Unknown
Inhibitor
Details
NefazodoneSodium-dependent dopamine transporterProteinHumans
Unknown
Inhibitor
Details
NefazodoneSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
NefazodoneSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
NomifensineSodium-dependent dopamine transporterProteinHumans
Unknown
Not AvailableDetails
NomifensineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Not AvailableDetails
NortriptylineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
NortriptylineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
ParoxetineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Details
ParoxetineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
ProtriptylineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
ProtriptylineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
SertralineSodium-dependent dopamine transporterProteinHumans
Unknown
Inhibitor
Binder
Details
SertralineSodium-dependent noradrenaline transporterProteinHumans
Unknown
Inhibitor
Downregulator
Details
SertralineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Binder
Downregulator
Details
TrazodoneSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
TrimipramineSodium-dependent dopamine transporterProteinHumans
Unknown
Inhibitor
Details
TrimipramineSodium-dependent noradrenaline transporterProteinHumans
Yes
Inhibitor
Details
TrimipramineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
VenlafaxineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details
VerapamilSodium-dependent serotonin transporterProteinHumans
Unknown
Unknown
Details
ZimelidineSodium-dependent serotonin transporterProteinHumans
Unknown
Not AvailableDetails
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AmitriptylineSodium-dependent noradrenaline transporterKi (nM)35N/AN/ADetails
AmoxapineSodium-dependent dopamine transporterKi (nM)4310N/AN/ADetails
AmoxapineSodium-dependent noradrenaline transporterKi (nM)16N/AN/ADetails
AmoxapineSodium-dependent serotonin transporterKi (nM)58N/AN/ADetails
BupropionSodium-dependent dopamine transporterKi (nM)520N/AN/ADetails
BupropionSodium-dependent noradrenaline transporterKi (nM)>10000N/AN/ADetails
CitalopramSodium-dependent serotonin transporterKi (nM)1.16N/AN/ADetails
ClomipramineSodium-dependent noradrenaline transporterKi (nM)38N/AN/ADetails
ClomipramineSodium-dependent serotonin transporterKi (nM)0.28N/AN/ADetails
DesipramineSodium-dependent noradrenaline transporterKi (nM)0.83N/AN/ADetails
DesipramineSodium-dependent serotonin transporterKi (nM)17.6N/AN/ADetails
DoxepinSodium-dependent noradrenaline transporterKi (nM)29.5N/AN/ADetails
DoxepinSodium-dependent serotonin transporterKi (nM)68N/AN/ADetails
FluoxetineSodium-dependent serotonin transporterKi (nM)0.81N/AN/ADetails
FluvoxamineSodium-dependent serotonin transporterKi (nM)2.2N/AN/ADetails
ImipramineSodium-dependent dopamine transporterKi (nM)8500N/AN/ADetails
ImipramineSodium-dependent noradrenaline transporterKi (nM)37N/AN/ADetails
ImipramineSodium-dependent serotonin transporterKi (nM)1.4N/AN/ADetails
MaprotilineSodium-dependent noradrenaline transporterKi (nM)11.1N/AN/ADetails
MianserinSodium-dependent dopamine transporterKi (nM)9400N/AN/ADetails
MianserinSodium-dependent noradrenaline transporterKi (nM)71N/AN/ADetails
MianserinSodium-dependent serotonin transporterKi (nM)4000N/AN/ADetails
NefazodoneSodium-dependent dopamine transporterKi (nM)360N/AN/ADetails
NefazodoneSodium-dependent noradrenaline transporterKi (nM)360N/AN/ADetails
NefazodoneSodium-dependent serotonin transporterKi (nM)200N/AN/ADetails
NomifensineSodium-dependent dopamine transporterKi (nM)56N/AN/ADetails
NomifensineSodium-dependent noradrenaline transporterKi (nM)15.6N/AN/ADetails
NomifensineSodium-dependent serotonin transporterKi (nM)1010N/AN/ADetails
NortriptylineSodium-dependent noradrenaline transporterKi (nM)4.37N/AN/ADetails
NortriptylineSodium-dependent serotonin transporterKi (nM)18N/AN/ADetails
ParoxetineSodium-dependent noradrenaline transporterKi (nM)40N/AN/ADetails
ParoxetineSodium-dependent serotonin transporterKi (nM)0.13N/AN/ADetails
ProtriptylineSodium-dependent noradrenaline transporterKi (nM)1.41N/AN/ADetails
ProtriptylineSodium-dependent serotonin transporterKi (nM)19.6N/AN/ADetails
TrazodoneSodium-dependent serotonin transporterKi (nM)160N/AN/ADetails
TrimipramineSodium-dependent dopamine transporterKi (nM)3780N/AN/ADetails
TrimipramineSodium-dependent noradrenaline transporterKi (nM)2450N/AN/ADetails
TrimipramineSodium-dependent serotonin transporterKi (nM)149N/AN/ADetails
VenlafaxineSodium-dependent dopamine transporterKi (nM)9300N/AN/ADetails
VenlafaxineSodium-dependent noradrenaline transporterKi (nM)1060N/AN/ADetails
VenlafaxineSodium-dependent serotonin transporterKi (nM)8.9N/AN/ADetails
ZimelidineSodium-dependent serotonin transporterKi (nM)152N/AN/ADetails