Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameNoradrenergic re-uptake    
Type of TargetSuccessful target    
Drug Potency against TargetPhentermineEC50 = 39.4 nM[1]
PhenmetrazineEC50 = 50 nM[2]
MazindolED50 = 1.5 nM[3]
MilnacipranIC50 = 100 nM[4]
TrimipramineIC50 = 1000 nM[5]
MilnacipranIC50 = 106 nM[6]
NortriptylineIC50 = 177 nM[7]
DiethylpropionIC50 = 18100 nM[8]
BupropionIC50 = 190000 nM[9]
VenlafaxineIC50 = 216000 nM[10]
DesipramineIC50 = 3.4 nM[11]
PhentermineIC50 = 39.4 nM[12]
ReboxetineIC50 = 8 nM[13]
PhenmetrazineKi = 131 nM[1]
BupropionKi = 1900 nM[14]
MazindolKi = 2.88 nM[1]
DuloxetineKi = 2400 nM[15]
NortriptylineKi = 2600 nM[15]
DuloxetineKi = 4.6 nM[4]
Desvenalfaxine succinateKi = 558.4 nM[16]
VenlafaxineKi = 640 nM[17]
DesipramineKi = 8.32 nM[1]
DesipraminepKi < 5[18]
DuloxetinepKi < 5[18]
NortriptylinepKi < 5[18]
ImipraminepKi < 5[18]
DOV-216303Ki = 20.3 nM[19]
DOV 21947Ki = 22.8 nM[20]
DOV-21947Ki = 22.8 nM[20]
Desvenlafaxine SRKi = 558.4 nM[16]
R-sibutramine metaboliteKi = 66 nM[21]
Action against Disease ModelSibutramineUptake of 3H-dopamine in rat whole brain synaptosomes IC50: 2000 nM[22]
Ref 1Curr Top Med Chem. 2006;6(17):1845-59.Therapeutic potential of monoamine transporter substrates. To Reference
Ref 2Eur J Pharmacol. 2002 Jun 28;447(1):51-7.Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. To Reference
Ref 3Eur J Pharmacol. 1977 Oct 15;45(4):329-33.Studies on the capacity of mazindol and dita to act as uptake inhibitors or releasing agents for 3H-biogenic amines in rat brain tissue slices. To Reference
Ref 4J Med Chem. 2005 Oct 20;48(21):6523-43.Designed multiple ligands. An emerging drug discovery paradigm. To Reference
Ref 5Psychopharmacology (Berl). 1977 Aug 16;53(3):309-14.Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. To Reference
Ref 6Biochem Pharmacol. 2005 Nov 1;70(9):1389-97.Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells. To Reference
Ref 7Mol Pharmacol. 1992 Nov;42(5):817-25.8-hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells. To Reference
Ref 8Bioorg Med Chem. 2000 Dec;8(12):2689-92.Uptake and release effects of diethylpropion and its metabolites with biogenic amine transporters. To Reference
Ref 9Mol Pharmacol. 2004 Sep;66(3):675-82.Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. To Reference
Ref 10Naunyn Schmiedebergs Arch Pharmacol. 2010 Jan;381(1):33-9. Epub 2009 Dec 10.Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics. To Reference
Ref 11J Med Chem. 2010 Jun 10;53(11):4511-21.Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231). To Reference
Ref 12J Pharmacol Exp Ther. 2003 Jun;305(3):1191-9. Epub 2003 Mar 20.(+)-Fenfluramine and its major metabolite, (+)-norfenfluramine, are potent substrates for norepinephrine transporters. To Reference
Ref 13Neuroendocrinology. 2004 Jan;79(1):54-62.Mirtazapine decreases stimulatory effects of reboxetine on cortisol, adrenocorticotropin and prolactin secretion in healthy male subjects. To Reference
Ref 14Nat Rev Drug Discov. 2008 Dec;7(12):989-1000.BCL-2 family antagonists for cancer therapy. To Reference
Ref 15Curr Drug Discov Technol. 2006 Mar;3(1):1-48.Development and validation of an in silico P450 profiler based on pharmacophore models. To Reference
Ref 16J Pharmacol Exp Ther. 2006 Aug;318(2):657-65. Epub 2006 May 4.Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. To Reference
Ref 17Nat Rev Drug Discov. 2009 Jul;8(7):547-66.Cell cycle kinases as therapeutic targets for cancer. To Reference
Ref 18Pharmacol Ther. 2006 May;110(2):135-370. Epub 2006 Mar 7.Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. To Reference
Ref 19J Clin Pharmacol. 2004 Dec;44(12):1360-7.DOV 216,303, a "triple" reuptake inhibitor: safety, tolerability, and pharmacokinetic profile. To Reference
Ref 20Eur J Pharmacol. 2003 Feb 14;461(2-3):99-104.Antidepressant-like actions of DOV 21,947: a "triple" reuptake inhibitor. To Reference
Ref 21Neuropharmacology. 1989 Feb;28(2):129-34.The contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride. To Reference
Ref 22Neurotox Res. 2001 Jul;3(3):235-47.Effects of sibutramine on the central dopaminergic system in rodents. To Reference


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