Norepinephrine transporter Inhibitors
14 drugsAbout Norepinephrine transporter
The Norepinephrine Transporter (NET), encoded by the SLC6A2 gene, regulates norepinephrine signaling by mediating its reuptake into presynaptic neurons. This process controls the concentration and duration of norepinephrine, a key neurotransmitter involved in various physiological functions.
NET is a significant drug target, supported by moderate genetic evidence linking SLC6A2 variants to diseases like orthostatic intolerance (score 0.64). Loss-of-function variants are associated with increased risk, suggesting activation of NET may be therapeutically beneficial.
NET is targeted by 14 FDA-approved small molecule drugs, including ADREVIEW, WELLBUTRIN XL and AUVELITY, spanning CNS, pain, and cardiovascular indications. Thirteen companies have approved drugs targeting NET, including GLENMARK PHARMS LTD and RUBICON RESEARCH.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Shoulder Pain with only 3 trials.
Human Genetic Evidence Moderate
Genetic evidence provides moderate support for NET as a drug target, with a maximum score of 0.64 for orthostatic intolerance.
Further investigation of activating NET may be warranted, given the association of loss-of-function variants with increased disease risk.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in cardiovascular disease, genetic, familial or congenital disease, nervous system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link SLC6A2 to 6 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 3 strong
max H4: 0.99eQTL/pQTL signals for SLC6A2 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top Drugs
Thirteen companies have approved drugs targeting NET, suggesting a moderately competitive landscape.
The presence of multiple players indicates relatively low barriers to entry, but also highlights the need for differentiation.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| CONTRAVE | NALPROPION | 2014 | 2 |
| TRAMADOL HYDROCHLORIDE | PH HEALTH | 2002 | 1 |
| QELBREE | SUPERNUS PHARMS | 2021 | 1 |
| CONCERTA | Johnson & Johnson | 2000 | 1 |
| ATOMOXETINE HYDROCHLORIDE | Apotex | 2010 | 1 |
| AUVELITY | AXSOME | 2022 | 1 |
| SAVELLA | AbbVie | 2009 | 1 |
| WELLBUTRIN SR | GSK | 1996 | 1 |
| FORFIVO XL | TWI PHARMS | 2011 | 1 |
| ADZENYS XR-ODT | NEOS THERAPS | 2016 | 1 |
| NORPRAMIN | VALIDUS PHARMS | 1964 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
Norepinephrine transporter is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage in targeting NET.
Clinical Trials 526 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 126 | 99 | 12 | 15 | 89% |
| Phase 2 | 130 | 87 | 18 | 25 | 83% |
| Phase 3 | 95 | 59 | 17 | 19 | 78% |
| Phase 4 | 175 | 120 | 25 | 29 | 83% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (1964 - 2022)
Attention-Deficit/Hyperactivity Disorder (ADHD)
The first NET-targeting drug was approved in 1964 (NORPRAMIN), with the most recent approval in 2022 (AUVELITY).
The continued approval of NET-targeting drugs suggests ongoing therapeutic relevance and potential for further innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 13 companies competing
- • Market share by company
Full Drug Portfolio
- • All 14 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 14-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 292 clinical trials targeting Norepinephrine transporter.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities