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.
Norepinephrine transporter 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 Norepinephrine transporter 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 |
|---|---|---|---|
| APLENZIN | BAUSCH | 2008 | 2 |
| TRAMADOL HYDROCHLORIDE | STRIDES PHARMA INTL | 2002 | 1 |
| ATOMOXETINE HYDROCHLORIDE | Teva | 2010 | 1 |
| FORFIVO XL | TWI PHARMS | 2011 | 1 |
| ADZENYS XR-ODT | NEOS THERAPS INC | 2016 | 1 |
| AUVELITY | AXSOME | 2022 | 1 |
| QELBREE | SUPERNUS PHARMS | 2021 | 1 |
| WELLBUTRIN SR | GSK | 1996 | 1 |
| NORPRAMIN | VALIDUS PHARMS | 1964 | 1 |
| CONCERTA | Johnson & Johnson | 2000 | 1 |
| SAVELLA | AbbVie | 2009 | 1 |
Norepinephrine transporter 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.
Norepinephrine transporter Clinical Trials 581 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Norepinephrine transporter. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 140 | 119 | 9 | 12 | 93% |
| Phase 2 | 152 | 104 | 27 | 21 | 79% |
| Phase 3 | 95 | 60 | 19 | 16 | 76% |
| Phase 4 | 194 | 125 | 33 | 36 | 79% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Norepinephrine transporter Drug Approval Timeline (1996 - 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
- • Sponsors: 319 (79 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on Norepinephrine transporter. A trial counts if an approved drug acting on Norepinephrine transporter is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.