Protein / target

Sodium-dependent noradrenaline transporter

SLC6A2P23975Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
84
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Neurotransmitter transmembrane transporter activity

Primary system

Nervous system

Strongest disease association

attention deficit-hyperactivity disorder

Clinical evidence · score 0.63

Therapeutic maturity

Clinically validated target

84 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

84 approved · 15 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818)

Subcellular location

Cell membraneCell projection, axonSynapse, synaptosome
Domains and Gene Ontology detail (26)

Gene Ontology

  • Caxon
  • Ccell surface
  • Cmembrane
  • Cneuronal cell body membrane
  • Cplasma membrane
  • Cpresynaptic membrane
  • Csynaptic vesicle membrane
  • Factin binding
  • Falpha-tubulin binding
  • Fbeta-tubulin binding
  • Fdopamine:sodium symporter activity
  • Fmetal ion binding

617 aa · 69 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOIon channel gatingGO
View supporting evidence

Synaptic signalling

  • ·Synapse, synaptosome
  • ·presynaptic membrane
  • ·chemical synaptic transmission
  • ·dopamine uptake involved in synaptic transmission

Ion channel gating

  • ·sodium ion transmembrane transport
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

STX1ASLC5A2ADCY7SLC22A3SLC18A2SCRT1SNCAADRA2AHTR1AYRDCSLC6A2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Amphetamine
Narrow target profileApprovedReleasing agent

Norepinephrine transporter releasing agent

Appears in clinical studies involving attention deficit-hyperactivity disorder, attention deficit-hyperactivity disorder, attention deficit-hyperactivity disorder, cocaine dependence

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

Duloxetine Hydrochloride
Narrow target profileApprovedInhibitor

Norepinephrine transporter inhibitor

Appears in clinical studies involving major depressive disorder, fibromyalgia, muscular disease, neuropathic pain

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

major depressive disorder1.00

Clinical · overall 0.62

attention deficit-hyperactivity disorder1.00

Clinical · overall 0.63

fibromyalgia0.99

Clinical · overall 0.60

depressive disorder0.99

Clinical · overall 0.61

Nasal congestion0.99

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

seasonal allergic rhinitis0.60

Clinical

obesity disorder0.60

Clinical

common cold0.60

Clinical

Pain0.60

Clinical

Obesity0.59

Clinical

Show all associations
attention deficit-hyperactivity disorder0.63
major depressive disorder0.62
depressive disorder0.61
fibromyalgia0.60
Nasal congestion0.60
seasonal allergic rhinitis0.60
obesity disorder0.60
common cold0.60
Pain0.60
Obesity0.59

Open Targets ranks 445 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 104 total

TAPENTADOLApproval

Pain · osteoarthritis · Low back pain

AMITRIPTYLINEApproval

depressive disorder · major depressive disorder · neuropathic pain

AMITIFADINEPhase 3

Obesity · major depressive disorder · alcohol dependence

BENZPHETAMINE HYDROCHLORIDEApproval

obesity disorder

SIBUTRAMINE HYDROCHLORIDEUnknown
NS-2359Phase 2

attention deficit-hyperactivity disorder · cocaine dependence · mood disorder

NORTRIPTYLINEApproval

depressive disorder · major depressive disorder · Pain

LEVOMILNACIPRAN HYDROCHLORIDEApproval

major depressive disorder · fibromyalgia · ischemic stroke

FAXELADOLPhase 2

fibromyalgia

AMOXAPINEApproval

major depressive disorder

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Safety liabilities

ventricular hypertrophydecreased sleepincreased heart rateincreased locomotor activityconstipationconstipationdecreased locomotor activitydrug abuse/dependencereceptor bindingincreased blood pressuredecreased paintachycardia

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

COMPLETED · via Amphetamine · NCT02020408

COMPLETED · via Duloxetine Hydrochloride · NCT01425827

COMPLETED · via Duloxetine Hydrochloride · NCT00067912

COMPLETED · via Duloxetine Hydrochloride · NCT00036309

COMPLETED · via Duloxetine Hydrochloride · NCT00479726

COMPLETED · via Amphetamine · NCT00733993

COMPLETED · via Duloxetine Hydrochloride · NCT05508516

COMPLETED · via Duloxetine Hydrochloride · NCT00071695

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

attention deficit-hyperactivity disorderWell supported
0.78
agreement 0.620.93
Clinical86%Literature14%

Open Targets aggregate 0.63 · 2 independent evidence families

major depressive disorderWell supported
0.77
agreement 0.610.93
Clinical90%Literature10%

Open Targets aggregate 0.62 · 2 independent evidence families

depressive disorderWell supported
0.75
agreement 0.600.91
Clinical95%Literature5%

Open Targets aggregate 0.61 · 2 independent evidence families

fibromyalgiaModerately supported
0.74
agreement 0.590.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

Nasal congestionModerately supported
0.74
agreement 0.570.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

12

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Product recall2026-06-04

    Recall (Class II): DULOXETINE HYDROCHLORIDE

    fda · safety · fda · via Duloxetine Hydrochloride

  2. Product recall2026-06-04

    Recall (Class II): DULOXETINE HYDROCHLORIDE

    fda · safety · fda · via Duloxetine Hydrochloride

  3. Product recall2025-07-15

    Recall (Class II): DULOXETINE HYDROCHLORIDE

    fda · safety · fda · via Duloxetine Hydrochloride

  4. New publication2025-04-28
    Astroglial CB<sub>1</sub> Reveal Sex-Specific Synaptic Effects of Amphetamine.

    Glia · 2025 · 3 citations · Europe PMC · via Amphetamine

  5. New publication2025-01-13
    Astrocytes Mediate Psychostimulant-Induced Alterations of Spike-Timing Dependent Synaptic Plasticity.

    Glia · 2025 · 2 citations · Europe PMC · via Amphetamine

  6. Product recall2024-12-06

    Recall (Class II): DULOXETINE HYDROCHLORIDE

    fda · safety · fda · via Duloxetine Hydrochloride

  7. New publication2014-04-14
    Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014 · 831 citations · Europe PMC · via Duloxetine Hydrochloride

  8. New publication2014-01-01
    Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

    Journal of addiction research & therapy · 2014 · 8 citations · Europe PMC · via Amphetamine

  9. New publication2011-10-01
    Animal models of schizophrenia.

    British journal of pharmacology · 2011 · 537 citations · Europe PMC · via Amphetamine

  10. New publication2010-11-01
    Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China.

    Chinese medical journal · 2010 · 27 citations · Europe PMC · via Duloxetine Hydrochloride

  11. New publication2010-09-21
    Efficacy and safety of duloxetine 60 mg and 120 mg daily in patients hospitalized for severe depression: a double-blind randomized trial.

    The Journal of clinical psychiatry · 2011 · 11 citations · Europe PMC · via Duloxetine Hydrochloride

  12. Regulatory approval2004-08-11

    Approval: Yentreve (EMA)

    ema · regulatory · ema · via Duloxetine Hydrochloride

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.