Target family: Monoamine transporter subfamily (type: transporter)
Target: NET

Ligand: amitriptyline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1961)
Primary target: yes
Median affinity: 6.480000019073486 pKi
Reference (Journal): An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Published in: Bioorg Med Chem Lett

Ligand: amoxapine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1980)
Primary target: yes
Median affinity: 7.889999866485596 pKi
Reference (Webpage): National Toxicology Program: Dept of Health and Human Services.

Ligand: atomoxetine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2002)
Primary target: yes
Median affinity: 8.6899995803833 pKd
Reference (Journal): Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
Published in: Bioorg Med Chem Lett

Ligand: bupropion (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1985)
Primary target: yes
Median affinity: 6.360000133514404 pKi
Reference (Journal): A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone.
Published in: Bioorg Med Chem

Ligand: citalopram (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1998)
Primary target: no
Median affinity: 3 pKi
Reference (Journal): A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter.
Published in: Bioorg Med Chem Lett

Ligand: clomipramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1989)
Primary target: yes
Median affinity: 7.420000076293945 pKd
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: desipramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (no history prior to 1964)
Primary target: yes
Median affinity: 8.680000305175781 pKi
Reference (Journal): 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).
Published in: J Med Chem

Ligand: desvenlafaxine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2008)
Primary target: yes
Median affinity: 6.190000057220459 pKi
Reference (Journal): Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor.
Published in: ACS Med Chem Lett

Ligand: dexamfetamine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1955, in complex; 1975 as Dextroamphetamine sulphate)
Primary target: yes
Median affinity: 7 pKi
Reference (Journal): An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Published in: Bioorg Med Chem Lett

Ligand: dexmethylphenidate (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2001)
Primary target: no
Median affinity: 6.570000171661377 pKi
Reference (Journal): Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate.
Published in: J Med Chem

Ligand: dosulepin (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: yes
Median affinity: 7.340000152587891 pKi
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: doxepin (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1969)
Primary target: yes
Median affinity: 7.539999961853027 pKi
Reference (Webpage): National Toxicology Program: Dept of Health and Human Services.

Ligand: duloxetine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA & EMA (2004)
Primary target: yes
Median affinity: 8.220000267028809 pKi
Reference (Journal): 4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: H05 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.170000076293945 pKi
Reference (Journal): Pharmacological Characterization of H05, a Novel Serotonin and Noradrenaline Reuptake Inhibitor with Moderate 5-HT<sub>2A</sub> Antagonist Activity for the Treatment of Depression.
Published in: J Pharmacol Exp Ther

Ligand: imipramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1959)
Primary target: yes
Median affinity: 7.800000190734863 pKi

Ligand: N-desalkylquetiapine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.920000076293945 pKi
Reference (Journal): N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity.
Published in: Neuropsychopharmacology

Ligand: levomilnacipran (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2013)
Primary target: yes
Median affinity: 7.400000095367432 pIC50
Reference (Journal): Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: lofepramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: yes
Median affinity: 8.270000457763672 pKi
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: maprotiline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1980)
Primary target: yes
Median affinity: 7.920000076293945 pKi
Reference (Journal): Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles.
Published in: Bioorg Med Chem

Ligand: mazindol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1973)
Primary target: no
Median affinity: 8.899999618530273 pKi

Ligand: methylphenidate (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1955)
Primary target: yes
Median affinity: 7.210000038146973 pIC50

Ligand: mianserin (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: no
Median affinity: 7.590000152587891 pKi
Reference (Journal): Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin.
Published in: J Med Chem

Ligand: milnacipran (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2009)
Primary target: yes
Median affinity: 9.100000381469727 pIC50
Reference (Journal): A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure-activity relationships.
Published in: Bioorg Med Chem Lett

Ligand: nefazodone (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1994)
Primary target: yes
Median affinity: 6.440000057220459 pKd
Reference (Journal): Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
Published in: Bioorg Med Chem Lett

Ligand: nisoxetine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pKi

Ligand: nomifensine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (approval date not specified, withdrawn 1992)
Primary target: yes
Median affinity: 8.100000381469727 pKi

Ligand: nortriptyline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1964)
Primary target: yes
Median affinity: 8.199999809265137 pKi
Reference (Journal): 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.
Published in: J Med Chem

Ligand: norzotepine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.960000038146973 pIC50
Reference (Journal): Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake.
Published in: J Pharmacol Exp Ther

Ligand: phenelzine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1961)
Primary target: no
Median affinity: 5 pKi
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: protriptyline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity: 8.850000381469727 pKd
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: protriptyline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity: 8.770000457763672 pIC50
Reference (Journal): First-in-class, dual-action, 3,5-disubstituted indole derivatives having human nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI) activity for the treatment of neuropathic pain.
Published in: J Med Chem

Ligand: protriptyline (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1967)
Primary target: yes
Median affinity: 8.170000076293945 pKi
Reference (Journal): cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
Published in: J Med Chem

Ligand: quetiapine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1997)
Primary target: no
Median affinity: 6.03000020980835 pKi
Reference (Journal): N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity.
Published in: Neuropsychopharmacology

Ligand: reboxetine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: yes
Median affinity: 8 pKi
Reference (Journal): Reboxetine: a pharmacologically potent, selective, and specific norepinephrine reuptake inhibitor.
Published in: Biol Psychiatry

Ligand: sibutramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1997)
Primary target: yes
Median affinity: 5.25 pKi
Reference (Webpage): National Toxicology Program: Dept of Health and Human Services.

Ligand: solriamfetol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2019), EMA (2020)
Primary target: no
Median affinity: 5.360000133514404 pIC50
Reference (Journal): Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.
Published in: J Pharmacol Exp Ther

Ligand: solriamfetol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2019), EMA (2020)
Primary target: no
Median affinity: 5.429999828338623 pKi
Reference (Journal): Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.
Published in: J Pharmacol Exp Ther

Ligand: [3H]mazindol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.300000190734863 pKd
Reference (Journal): Binding of [3H]mazindol to cardiac norepinephrine transporters: kinetic and equilibrium studies.
Published in: Naunyn Schmiedebergs Arch Pharmacol

Ligand: [3H]nisoxetine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pKd

Ligand: tapentadol (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2008)
Primary target: yes
Median affinity: 5.059999942779541 pKi
Reference (Journal): (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties.
Published in: J Pharmacol Exp Ther

Ligand: toludesvenlafaxine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: China (2022)
Primary target: no
Median affinity: 6.119999885559082 pIC50
Reference (Journal): Correction to "Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges".
Published in: J Med Chem

Ligand: trimipramine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1979)
Primary target: yes
Median affinity: 5.610000133514404 pKi
Reference (Journal): Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Published in: Eur J Pharmacol

Ligand: venlafaxine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (1993)
Primary target: yes
Median affinity: 6.269999980926514 pIC50
Reference (Journal): Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: ziprasidone (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2001)
Primary target: no
Median affinity: 7.320000171661377 pKi
Reference (Journal): Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one.
Published in: Bioorg Med Chem

Ligand: zotepine (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Primary target: no
Median affinity: 7.150000095367432 pIC50
Reference (Journal): Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake.
Published in: J Pharmacol Exp Ther