DGIdb - SLC6A2 Gene Record

SLC6A2 6530 Druggable Genome

Alternate Names:

6530
SOLUTE CARRIER FAMILY 6 MEMBER 2
SLC6A2
NAT1
NET
NET1
SLC6A5
163970
11048
ENSG00000103546
OTTHUMG00000133208
P23975
SC6A2_HUMAN
PA310
SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET). [SOURCE:UNIPROT/SWISSPROT;ACC:P23975]
SODIUM-DEPENDENT NORADRENALINE TRANSPORTER
Norepinephrine transporter
SLCA2

Gene Info:

Human Readable Name	DRUGGABLE GENOME
Target Subclass	Other
Target Subclass	SLC
Target Subclass	SLC6
Target Main Class	Transporters
Transmembrane Helix Count	12
Interpro Short Name	Na/ntran_symport
Interpro Acc	IPR000175
Uniprot Status	Swiss-Prot
Interpro Name	Sodium:neurotransmitter symporter
Human Readable Name	TRANSPORTER
Interpro Type	Family
Uniprot Evidence	1: Evidence at protein level
Target Class	Transporters
Target Subclass	TC:2.A.22.1.2
Gene Biotype	PROTEIN_CODING

(7 More Sources)

Gene Categories: Category Details

TRANSPORTER
CELL SURFACE
DRUGGABLE GENOME

Publications:

Arias et al., 2009, Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion., Int. Rev. Neurobiol.
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Saba et al., 2007, [11C]LBT-999: a suitable radioligand for investigation of extra-striatal dopamine transporter with PET., Synapse
Arai et al., 2003, Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics., Brain Res.
Cloonan et al., 2010, The antidepressants maprotiline and fluoxetine have potent selective antiproliferative effects against Burkitt lymphoma independently of the norepinephrine and serotonin transporters., Leuk. Lymphoma
Dronjak et al., 2007, Effects of noradrenaline and serotonin reuptake inhibitors on pituitary-adrenocortical and sympatho-adrenomedullar system of adult rats., Neuro Endocrinol. Lett.
Mochizucki, 2004, Serotonin and noradrenaline reuptake inhibitors in animal models of pain., Hum Psychopharmacol
Sagata et al., 2002, Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells., Anesth. Analg.
Frink et al., 1996, Influence of tramadol on neurotransmitter systems of the rat brain., Arzneimittelforschung
Berrocoso et al., 2009, Cooperative opioid and serotonergic mechanisms generate superior antidepressant-like effects in a mice model of depression., Int. J. Neuropsychopharmacol.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Barakat A, 2019, Revisiting Tramadol: A Multi-Modal Agent for Pain Management., CNS Drugs
Garnock-Jones et al., 2009, Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents., Paediatr Drugs
Biederman et al., 2002, Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder., Pediatrics
Michelson et al., 2003, Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies., Biol. Psychiatry
Spencer et al., 2002, Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder., J Clin Psychiatry
Wernicke et al., 2003, Cardiovascular effects of atomoxetine in children, adolescents, and adults., Drug Saf
Tatsumi et al., 1997, Pharmacological profile of antidepressants and related compounds at human monoamine transporters., Eur. J. Pharmacol.
Kaplan et al., 2004, Efficacy and safety of atomoxetine in childhood attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder., J Atten Disord
Wernicke et al., 2004, Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment., J Clin Psychopharmacol
Purper-Ouakil et al., [Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents]., Encephale
Gaillez et al., 2007, [Atomoxetine (Strattera), an alternative in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children]., Encephale
Yang L et al., 2013, Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children., J Neural Transm (Vienna)
Ramoz N et al., 2009, A haplotype of the norepinephrine transporter (Net) gene Slc6a2 is associated with clinical response to atomoxetine in attention-deficit hyperactivity disorder (ADHD)., Neuropsychopharmacology
Yu G et al., 2016, Atomoxetine: A Review of Its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition., J Child Adolesc Psychopharmacol
Zhao et al., Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat., Neurotoxicol Teratol
Carrera et al., 2004, Cocaine pharmacology and current pharmacotherapies for its abuse., Bioorg. Med. Chem.
Burchett et al., 1997, Serotonin, dopamine and norepinephrine transporter mRNAs: heterogeneity of distribution and response to 'binge' cocaine administration., Brain Res. Mol. Brain Res.
Galli et al., 1995, Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants., J. Exp. Biol.
Kantor et al., 2001, Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells., J. Pharmacol. Exp. Ther.
Tatsumi et al., 1999, Pharmacological profile of neuroleptics at human monoamine transporters., Eur. J. Pharmacol.
Anton et al., 2004, Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells., J Gene Med
Dziedzicka-Wasylewska et al., 2006, Effect of antidepressant drugs in mice lacking the norepinephrine transporter., Neuropsychopharmacology
Mitchell et al., 2006, The effects of norepinephrine transporter inactivation on locomotor activity in mice., Biol. Psychiatry
Haenisch B et al., 2011, Inhibitory potencies of trimipramine and its main metabolites at human monoamine and organic cation transporters., Psychopharmacology (Berl)
Stahl et al., 2004, A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor., Prim Care Companion J Clin Psychiatry
Bondarev et al., 2003, Behavioral and biochemical investigations of bupropion metabolites., Eur. J. Pharmacol.
Shalabi AR et al., 2017, Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release., ACS Chem Neurosci
Mortensen OV et al., 2006, Gain of function mutants reveal sites important for the interaction of the atypical inhibitors benztropine and bupropion with monoamine transporters., J Neurochem
Jungkun et al., 2001, Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans., J Neural Transm (Vienna)
Galli et al., 1996, Norepinephrine transporters have channel modes of conduction., Proc. Natl. Acad. Sci. U.S.A.
Joyce et al., 2001, Interaction of local anaesthetic agents with the endogenous norepinephrine transporter in SH-SY5Y human neuroblastoma cells., Neurosci. Lett.
Yi et al., 2005, Alpha-adrenergic modulation of synaptic transmission in rabbit pancreatic ganglia., Auton Neurosci
Barker et al., 1996, Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter., Mol. Pharmacol.
Roubert et al., 2001, A Na(+)/Cl(-)-dependent transporter for catecholamines, identified as a norepinephrine transporter, is expressed in the brain of the teleost fish medaka (Oryzias latipes)., Mol. Pharmacol.
Roubert et al., 2001, Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity., J. Biol. Chem.
Vaishnavi et al., 2004, Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity., Biol. Psychiatry
Kim et al., 2006, Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression., JAMA
Reddy et al., 2010, Clinical utility of desvenlafaxine 50 mg/d for treating MDD: a review of two randomized placebo-controlled trials for the practicing physician., Curr Med Res Opin
Liebowitz et al., 2010, Efficacy, safety, and tolerability of Desvenlafaxine 50 mg/d for the treatment of major depressive disorder:a systematic review of clinical trials., Prim Care Companion J Clin Psychiatry
Perry et al., 2009, Desvenlafaxine: a new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder., Clin Ther
Mason et al., 2007, Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter., J. Pharmacol. Exp. Ther.
Deecher et al., 2006, Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor., J. Pharmacol. Exp. Ther.
Kamath et al., 2008, Desvenlafaxine succinate for major depressive disorder: a critical review of the evidence., Expert Rev Neurother
Angyal N et al., 2018, Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients., Prog Neuropsychopharmacol Biol Psychiatry
Myer NM et al., 2018, Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD., Mol Psychiatry
Kim BN et al., 2013, Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder., J Clin Psychopharmacol
Hong SB et al., 2012, Dopaminergic and noradrenergic gene polymorphisms and response to methylphenidate in korean children with attention-deficit/hyperactivity disorder: is there an interaction?, J Child Adolesc Psychopharmacol
Gray et al., 2007, Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress., J. Neurosci.
Chuhan et al., 2006, Impairment of single-trial memory formation by oral methylphenidate in the rat., Neurobiol Learn Mem
Sandoval et al., 2001, Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model., J. Neurosci.
Yang et al., 2004, Association of norepinephrine transporter gene with methylphenidate response., J Am Acad Child Adolesc Psychiatry
Williard et al., 2007, Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity., Behav Pharmacol
Tilley et al., 2008, The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter., J. Pharmacol. Exp. Ther.
Berridge CW et al., 2006, Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function., Biol Psychiatry
Markowitz JS et al., 2006, A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study., J Child Adolesc Psychopharmacol
Dlugos et al., 2009, Further evidence of association between amphetamine response and SLC6A2 gene variants., Psychopharmacology (Berl.)
Dlugos et al., 2007, Norepinephrine transporter gene variation modulates acute response to D-amphetamine., Biol. Psychiatry
Burnette et al., 1996, Human norepinephrine transporter kinetics using rotating disk electrode voltammetry., Anal. Chem.
Larsen MH et al., 2007, Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine., Eur J Pharmacol
Bryson HM et al., 1996, Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states., Drugs Aging
Marshe VS et al., 2017, Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults., Am J Psychiatry
Van Ameringen et al., 2009, Pharmacotherapy for social anxiety disorder: an update., Isr J Psychiatry Relat Sci
Westenberg, 2009, Recent advances in understanding and treating social anxiety disorder., CNS Spectr
Béïque et al., 1998, Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters., Eur. J. Pharmacol.
Béïque et al., 2000, Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat., Neuropharmacology
Sindrup et al., 2005, Antidepressants in the treatment of neuropathic pain., Basic Clin. Pharmacol. Toxicol.
Bymaster et al., 2001, Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors., Neuropsychopharmacology
Rothman et al., 2002, Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain., Eur. J. Pharmacol.
Rothman et al., 2006, Therapeutic potential of monoamine transporter substrates., Curr Top Med Chem
Heusser et al., 2006, Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects., Clin. Pharmacol. Ther.
Gomis Barbará, [Pharmacological treatment of obesity]., Rev Med Univ Navarra
Birkenfeld et al., 2005, Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients--sibutramine and blood pressure., Clin. Auton. Res.
Jordan et al., 2005, Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials., Int J Obes (Lond)
Birkenfeld et al., 2002, Paradoxical effect of sibutramine on autonomic cardiovascular regulation., Circulation
Krahn et al., 2001, Narcolepsy and obesity: remission of severe cataplexy with sibutramine., Sleep Med.
Tziomalos et al., 2009, The use of sibutramine in the management of obesity and related disorders: an update., Vasc Health Risk Manag
Berke et al., 2000, Medical management of obesity., Am Fam Physician
Heusser et al., 2007, Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment., J. Clin. Endocrinol. Metab.
Sharma et al., 2008, Sibutramine: current status as an anti-obesity drug and its future perspectives., Expert Opin Pharmacother
Markowitz et al., 2008, Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?, J Clin Psychopharmacol
Davids et al., 2002, Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning., Psychopharmacology (Berl.)
Ding et al., 1997, Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain., Psychopharmacology (Berl.)
Wee et al., 2004, Reinforcing effect of pseudoephedrine isomers and the mechanism of action., Eur. J. Pharmacol.
Foley et al., 2002, Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers., J Neural Transm (Vienna)
Paczkowski FA et al., 2007, chi-Conotoxin and tricyclic antidepressant interactions at the norepinephrine transporter define a new transporter model., J Biol Chem
Weinshenker et al., 2002, Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo., Brain Res.
Bryan-Lluka et al., 2003, chi-Conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter., J. Biol. Chem.
Zavosh et al., 1999, Desipramine treatment decreases 3H-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells., Brain Res. Bull.
Zhu et al., 2004, The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function., Neurochem. Res.
Ordway et al., 2005, Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation., J. Neurosci. Methods
Proietto et al., 2000, Novel anti-obesity drugs., Expert Opin Investig Drugs
Stephens et al., 2005, Phentermine and anaesthesia., Anaesth Intensive Care
Samanin et al., 1993, Neurochemical mechanism of action of anorectic drugs., Pharmacol. Toxicol.
Tzschentke et al., 2007, (-)-(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., J. Pharmacol. Exp. Ther.
Hunziker et al., 2005, Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder., Clin Ther
Karpa et al., 2002, Duloxetine pharmacology: profile of a dual monoamine modulator., CNS Drug Rev
Gould et al., 2007, Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain., Biol. Psychiatry
Trivedi et al., 2008, Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine., Int Clin Psychopharmacol
van Groeningen et al., 1989, Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer., Eur J Cancer Clin Oncol
Jost et al., 2004, Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus., Clin. Auton. Res.
Schou et al., 2005, Post-mortem human brain autoradiography of the norepinephrine transporter using (S,S)-[18F]FMeNER-D2., Eur Neuropsychopharmacol
Vincent et al., 2004, Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles., Circulation
Mirza et al., 2007, Serotonin transporter density and anxiolytic-like effects of antidepressants in mice., Prog. Neuropsychopharmacol. Biol. Psychiatry
Bymaster et al., 2005, The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression., Curr. Pharm. Des.
Khullar et al., 2010, Mixed incontinence: current evidence and future perspectives., Neurourol. Urodyn.
Carter et al., 2009, Duloxetine: a review of its use in the treatment of generalized anxiety disorder., CNS Drugs
Sulzer et al., 2005, Mechanisms of neurotransmitter release by amphetamines: a review., Prog. Neurobiol.
Fleckenstein et al., 2007, New insights into the mechanism of action of amphetamines., Annu. Rev. Pharmacol. Toxicol.
Cheetham et al., 1996, [3H]nisoxetine--a radioligand for noradrenaline reuptake sites: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatments., Neuropharmacology
Davis et al., 1997, Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression., Drugs
Taylor et al., 1995, Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug., J Clin Psychiatry
Owen et al., 1999, Norepinephrine transporter gene polymorphism is not associated with susceptibility to major depression., Psychiatry Res
Owens et al., 1995, The serotonergic antidepressant nefazodone inhibits the serotonin transporter: in vivo and ex vivo studies., Life Sci.
Baladi MG et al., 2018, Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor., J Pharmacol Exp Ther
Stahl, 2008, Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines., CNS Spectr
Leo et al., 2006, Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain., Curr Opin Investig Drugs
Moret et al., 1985, Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug., Neuropharmacology
Timple JM et al., 2013, The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities., J Nat Prod
Hampel T et al., 2014, Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells., Bioorg Med Chem Lett

DEXMETHYLPHENIDATE SLC6A2

Interaction Score: 8.72

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Focalin

Novel drug target Established target

PMIDs:
17611273 18480678 9537821 16246598 11160413 11862378 15322419 17218796 9181638 18698001

Sources:
TdgClinicalTrial
ATOMOXETINE SLC6A2

Interaction Score: 8.46

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name atomoxetine hydrochloride,Strattera

Novel drug target Established target

PMIDs:
19445548 12456942 12547466 12523874 12862507 9537821 15801334 14709944 16142049 18033153 23266789 19387424 26859445

Sources:
TdgClinicalTrial TEND PharmGKB
GUANETHIDINE SLC6A2

Interaction Score: 7.93

Interaction Types & Directionality:

inducer (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
8710929 11403930 16126010

Sources:
TdgClinicalTrial TEND
PHENMETRAZINE SLC6A2

Interaction Score: 4.76

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
12106802 17016423 17139284 17017961

Sources:
TdgClinicalTrial TEND
SIBUTRAMINE SLC6A2

Interaction Score: 4.12

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name sibutramine HCl monohydrate,Meridia, Reductil, Reduxade, Zelium

PMIDs:
16678551 15382615 15944869 15685250 12417543 11152984 11752352 19475780 10929704 17284621 18671470

Sources:
TdgClinicalTrial TEND
DIETHYLPROPION SLC6A2

Interaction Score: 3.96

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
19897080 17016423 17139284

Sources:
TdgClinicalTrial TEND
PHENTERMINE SLC6A2

Interaction Score: 2.77

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
11060745 16119498 17016423 17139284 7902561

Sources:
TdgClinicalTrial TEND
DESVENLAFAXINE SLC6A2

Interaction Score: 2.54

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name Pristiq

PMIDs:
19919295 20944767 19698900 17673606 16675639 19086875

Sources:
TdgClinicalTrial TEND
SOLRIAMFETOL SLC6A2

Interaction Score: 1.59

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name YKP-10A

Novel drug target Established target

PMIDs:
29891587

Sources:
TdgClinicalTrial
DULOXETINE SLC6A2

Interaction Score: 1.59

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Cymbalta

Novel drug target Established target

PMIDs:
16199241 12481192 16650830 18408530 2784100 14744476 15316838 16139169 15184278 17335951 11752352 15892657 20432324 19480470 9669506

Sources:
TdgClinicalTrial TEND
PROTRIPTYLINE SLC6A2

Interaction Score: 1.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
8684598 17016423 17139284 9537821

Sources:
TdgClinicalTrial TEND
TRIMIPRAMINE SLC6A2

Interaction Score: 1.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
17016423 17139284 9537821 21484238

Sources:
TdgClinicalTrial TEND
MILNACIPRAN SLC6A2

Interaction Score: 1.27

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Milnacipran

Novel drug target Established target

PMIDs:
16869117 3005901

Sources:
TdgClinicalTrial TEND
DESIPRAMINE SLC6A2

Interaction Score: 1.27

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
17428804 12137927 12837768 10424850 15002740 9537821 11752352 15814154

Sources:
DTC TdgClinicalTrial TEND PharmGKB
VENLAFAXINE SLC6A2

Interaction Score: 1.27

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Effexor

Novel drug target Established target

PMIDs:
28068779 19728573 16893531 14744476 19238127 9669506 10884561 15910402 11750180

Sources:
TdgClinicalTrial TEND PharmGKB
NORTRIPTYLINE SLC6A2

Interaction Score: 1.15

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name CRx-170

Novel drug target Established target

Trial Name CRx-191

PMIDs:
8863842 11502876 9537821 11092898 14744476 17018806

Sources:
TdgClinicalTrial TEND
NEFAZODONE SLC6A2

Interaction Score: 1.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
9098663 9537821 7649970 10512149 7475971

Sources:
TdgClinicalTrial TEND
HINOKININ SLC6A2

Interaction Score: 1.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24112084

Sources:
DTC
TESOFENSINE SLC6A2

Interaction Score: 1.06

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Established target

Trial Name tesofensine, NS-2330

PMIDs:
17112503

Sources:
TdgClinicalTrial
DEXTROAMPHETAMINE SLC6A2

Interaction Score: 1.06

Interaction Types & Directionality:

negative modulator (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name SLI 381, SPD 465,Adderall, Adderall XR, Adderall IR

PMIDs:
19727679 17239355 8794928

Sources:
TdgClinicalTrial
IMIPRAMINE SLC6A2

Interaction Score: 1.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
11356924 10193665 14716684 16554743 16893531

Sources:
TdgClinicalTrial TEND
MAPROTILINE SLC6A2

Interaction Score: 1.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
17068778 12573515 20141432 17984940 15378668

Sources:
TdgClinicalTrial TEND
IOBENGUANE SLC6A2

Interaction Score: 0.79

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24814532

Sources:
DTC
LEVOMILNACIPRAN SLC6A2

Interaction Score: 0.79

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name levomilnacipran, F2695

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial
EDIVOXETINE SLC6A2

Interaction Score: 0.79

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Established target

Trial Name LY-2216684

PMIDs:
None found

Sources:
TdgClinicalTrial
BUPROPION SLC6A2

Interaction Score: 0.75

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name BVF-033,Aplenzin

Novel drug target Established target

Trial Name Contrave

PMIDs:
15361919 12909199 16893531 11752352 28220701 16923164

Sources:
TdgClinicalTrial TEND
TAPENTADOL SLC6A2

Interaction Score: 0.63

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name tapentadol

Novel drug target Established target

PMIDs:
17656655

Sources:
TdgClinicalTrial
TRAMADOL SLC6A2

Interaction Score: 0.62

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name PTI-601

Novel drug target Established target

Trial Name tramadol extended-release,Raliva ER

PMIDs:
11916794 8955860 19341511 11752352 31004280

Sources:
TdgClinicalTrial TEND
AMITRIPTYLINE SLC6A2

Interaction Score: 0.61

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name OMS-103HP

Novel drug target Established target

Trial Name amitriptyline + ketamine,Epicept NP-1

PMIDs:
14744476 9537821 8736630

Sources:
TdgClinicalTrial TEND
AMOXAPINE SLC6A2

Interaction Score: 0.57

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name CRx-119

Novel drug target Established target

Trial Name CRx-150, amoxapine plus dipyridamole

PMIDs:
17016423 17139284 9537821

Sources:
TdgClinicalTrial TEND
METHYLPHENIDATE SLC6A2

Interaction Score: 0.56

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name methylphenidate HCl,Ritalin LA

Trial Name methylphenidate HCl,Metadate CD, Equasym

Novel drug target Established target

PMIDs:
29374517 29230023 23609393 23083021 17611273 9537821 16246598 11160413 15322419 17218796 18698001 16806100 17201613

Sources:
TdgClinicalTrial TEND PharmGKB
CLOMIPRAMINE SLC6A2

Interaction Score: 0.53

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
9537821 11341486

Sources:
TdgClinicalTrial TEND
COCAINE SLC6A2

Interaction Score: 0.45

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
15113605 15351386 9387868 7500004

Sources:
TdgClinicalTrial TEND
BETHANIDINE SLC6A2

Interaction Score: 0.4

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial TEND
DOXEPIN SLC6A2

Interaction Score: 0.35

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name doxepin nasal solution,Dolorac

Novel drug target Established target

Trial Name Silenor (SO-101)

PMIDs:
19179941 9537821

Sources:
TdgClinicalTrial TEND
PSEUDOEPHEDRINE SLC6A2

Interaction Score: 0.28

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name fexofenadine + ps/

Novel drug target Established target

PMIDs:
15189772 12373557

Sources:
TdgClinicalTrial
METHAMPHETAMINE SLC6A2

Interaction Score: 0.18

Interaction Types & Directionality:

negative modulator (inhibitory)

Interaction Info:

Trial Name low dose intravenous methamphetamine

Novel drug target Established target

PMIDs:
15955613 17209801

Sources:
TdgClinicalTrial
TEDATIOXETINE SLC6A2

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name Lu AA24530

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial
TRAZODONE SLC6A2

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TEND

Ensembl: ENSG00000103546
- Version: 101_38
Alternate Names:

SLC6A2 Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
TdgClinicalTrial: P23975
- Version: January-2014
Alternate Names:

SLC6A2 Gene Symbol

SLCA2 Gene Symbol

Gene Info:

Target Class Transporters

Target Subclass TC:2.A.22.1.2

Publications:
RussLampel: ENSG00000103546
- Version: 26-July-2011
Alternate Names:

SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET). [SOURCE:UNIPROT/SWISSPROT;ACC:P23975] Description

ENSG00000103546 Ensembl Gene Id

SLC6A2 Display Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:
HopkinsGroom: P23975
- Version: 11-September-2012
Alternate Names:

6530 Entrez Gene Id

SC6A2_HUMAN Uniprot Id

SLC6A2 Uniprot Gene Name

Gene Info:

Interpro Short Name Na/ntran_symport

Human Readable Name DRUGGABLE GENOME

Interpro Acc IPR000175

Gene Categories:

TRANSPORTER, DRUGGABLE GENOME

Publications:
TEND: P23975
- Version: 01-August-2011
Alternate Names:

6530 Entrez Gene Id

SLC6A2 Gene Symbol

P23975 Uniprot Accession

Gene Info:

Target Subclass Other

Target Subclass SLC

Target Subclass SLC6

Publications:

PharmGKB: SLC6A2

Version: 18-August-2020

Alternate Names:

PA310 PharmGKB ID

Gene Info:

Publications:

Ramoz N et al., 2009, A haplotype of the norepinephrine transporter (Net) gene Slc6a2 is associated with clinical response to atomoxetine in attention-deficit hyperactivity disorder (ADHD)., Neuropsychopharmacology

Yang L et al., 2013, Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children., J Neural Transm (Vienna)

Marshe VS et al., 2017, Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults., Am J Psychiatry

NCI: SLC6A2
- Version: 14-September-2017
Alternate Names:

Gene Info:

Publications:

Xiao et al., 1995, Acute administration of alpha-methyl-para-tyrosine alters levels of norepinephrine transporter mRNA in the rat brainstem., Brain Res. Mol. Brain Res.

DTC: SLC6A2

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Hampel T et al., 2014, Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells., Bioorg Med Chem Lett

Paczkowski FA et al., 2007, chi-Conotoxin and tricyclic antidepressant interactions at the norepinephrine transporter define a new transporter model., J Biol Chem

Timple JM et al., 2013, The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities., J Nat Prod

HingoraniCasas: ENSG00000103546
- Version: 31-May-2017
Alternate Names:

ENSG00000103546 Gene Symbol

SLC6A2 Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
GO: SLC6A2
- Version: 01-February-2022
Alternate Names:

NAT1 GO Gene Synonym

NET1 GO Gene Synonym

SLC6A5 GO Gene Synonym

Gene Info:

Gene Categories:

CELL SURFACE

Publications:
Pharos: SLC6A2
- Version: 01-February-2022
Alternate Names:

Sodium-dependent noradrenaline transporter Gene Name

P23975 UniProt ID

Gene Info:

Gene Categories:

TRANSPORTER

Publications:

Trial Name	atomoxetine hydrochloride,Strattera
Novel drug target	Established target

Trial Name	CRx-170
Novel drug target	Established target
Trial Name	CRx-191

Trial Name	levomilnacipran, F2695
Novel drug target	Established target

Trial Name	BVF-033,Aplenzin
Novel drug target	Established target
Trial Name	Contrave

Trial Name	PTI-601
Novel drug target	Established target
Trial Name	tramadol extended-release,Raliva ER

Trial Name	OMS-103HP
Novel drug target	Established target
Trial Name	amitriptyline + ketamine,Epicept NP-1

Trial Name	CRx-119
Novel drug target	Established target
Trial Name	CRx-150, amoxapine plus dipyridamole

Trial Name	methylphenidate HCl,Ritalin LA
Trial Name	methylphenidate HCl,Metadate CD, Equasym
Novel drug target	Established target

Trial Name	doxepin nasal solution,Dolorac
Novel drug target	Established target
Trial Name	Silenor (SO-101)

Trial Name	fexofenadine + ps/
Novel drug target	Established target

Trial Name	low dose intravenous methamphetamine
Novel drug target	Established target

SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET). [SOURCE:UNIPROT/SWISSPROT;ACC:P23975]	Description
ENSG00000103546	Ensembl Gene Id
SLC6A2	Display Id

6530	Entrez Gene Id
SC6A2_HUMAN	Uniprot Id
SLC6A2	Uniprot Gene Name

Sodium-dependent noradrenaline transporter	Gene Name
P23975	UniProt ID

SLC6A2 Gene Record

SLC6A2 6530 Druggable Genome

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Focalin Novel drug target Established target

PMIDs: 17611273 18480678 9537821 16246598 11160413 11862378 15322419 17218796 9181638 18698001

Sources: TdgClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name atomoxetine hydrochloride,Strattera Novel drug target Established target

PMIDs: 19445548 12456942 12547466 12523874 12862507 9537821 15801334 14709944 16142049 18033153 23266789 19387424 26859445

Sources: TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality: inducer (activating)

Interaction Info: Novel drug target Established target Trial Name -

PMIDs: 8710929 11403930 16126010

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 12106802 17016423 17139284 17017961

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Novel drug target Established target Trial Name sibutramine HCl monohydrate,Meridia, Reductil, Reduxade, Zelium

PMIDs: 16678551 15382615 15944869 15685250 12417543 11152984 11752352 19475780 10929704 17284621 18671470

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 19897080 17016423 17139284

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Novel drug target Established target Trial Name -

PMIDs: 11060745 16119498 17016423 17139284 7902561

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Novel drug target Established target Trial Name Pristiq

PMIDs: 19919295 20944767 19698900 17673606 16675639 19086875

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name YKP-10A Novel drug target Established target

PMIDs: 29891587

Sources: TdgClinicalTrial

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Cymbalta Novel drug target Established target

PMIDs: 16199241 12481192 16650830 18408530 2784100 14744476 15316838 16139169 15184278 17335951 11752352 15892657 20432324 19480470 9669506

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 8684598 17016423 17139284 9537821

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 17016423 17139284 9537821 21484238

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Milnacipran Novel drug target Established target

PMIDs: 16869117 3005901

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 17428804 12137927 12837768 10424850 15002740 9537821 11752352 15814154

Sources: DTC TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name Effexor Novel drug target Established target

PMIDs: 28068779 19728573 16893531 14744476 19238127 9669506 10884561 15910402 11750180

Sources: TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name CRx-170 Novel drug target Established target Trial Name CRx-191

PMIDs: 8863842 11502876 9537821 11092898 14744476 17018806

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 9098663 9537821 7649970 10512149 7475971

Sources: TdgClinicalTrial TEND

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24112084

Sources: DTC

Interaction Types & Directionality: n/a

Interaction Info: Novel drug target Established target Trial Name tesofensine, NS-2330

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Focalin

Novel drug target Established target

PMIDs:
17611273 18480678 9537821 16246598 11160413 11862378 15322419 17218796 9181638 18698001

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name atomoxetine hydrochloride,Strattera

Novel drug target Established target

PMIDs:
19445548 12456942 12547466 12523874 12862507 9537821 15801334 14709944 16142049 18033153 23266789 19387424 26859445

Sources:
TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality:

inducer (activating)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
8710929 11403930 16126010

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
12106802 17016423 17139284 17017961

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name sibutramine HCl monohydrate,Meridia, Reductil, Reduxade, Zelium

PMIDs:
16678551 15382615 15944869 15685250 12417543 11152984 11752352 19475780 10929704 17284621 18671470

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
19897080 17016423 17139284

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
11060745 16119498 17016423 17139284 7902561

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name Pristiq

PMIDs:
19919295 20944767 19698900 17673606 16675639 19086875

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name YKP-10A

Novel drug target Established target

PMIDs:
29891587

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Cymbalta

Novel drug target Established target

PMIDs:
16199241 12481192 16650830 18408530 2784100 14744476 15316838 16139169 15184278 17335951 11752352 15892657 20432324 19480470 9669506

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
8684598 17016423 17139284 9537821

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
17016423 17139284 9537821 21484238

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Milnacipran

Novel drug target Established target

PMIDs:
16869117 3005901

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
17428804 12137927 12837768 10424850 15002740 9537821 11752352 15814154

Sources:
DTC TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name Effexor

Novel drug target Established target

PMIDs:
28068779 19728573 16893531 14744476 19238127 9669506 10884561 15910402 11750180

Sources:
TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name CRx-170

Novel drug target Established target

Trial Name CRx-191

PMIDs:
8863842 11502876 9537821 11092898 14744476 17018806

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
9098663 9537821 7649970 10512149 7475971

Sources:
TdgClinicalTrial TEND

Interaction Types & Directionality:

n/a

PMIDs:
24112084

Sources:
DTC

Interaction Types & Directionality:

n/a

Interaction Info:

Novel drug target Established target

Trial Name tesofensine, NS-2330

PMIDs:
17112503

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

negative modulator (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name SLI 381, SPD 465,Adderall, Adderall XR, Adderall IR

PMIDs:
19727679 17239355 8794928

Sources:
TdgClinicalTrial

Interaction Types & Directionality:

inhibitor (inhibitory)