Dopamine transporter Inhibitors
8 drugsAbout Dopamine transporter
The Dopamine transporter (DAT), encoded by SLC6A3, regulates dopamine levels in the synaptic cleft by reabsorbing dopamine into presynaptic neurons. This process controls dopaminergic neurotransmission, which is vital for neurological and psychiatric functions.
Human genetic studies provide strong validation for targeting DAT, with variants linked to classic dopamine transporter deficiency syndrome (score 0.85) and infantile dystonia-parkinsonism (score 0.83). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
DAT is targeted by 8 FDA-approved small molecule drugs, including WELLBUTRIN XL, APLENZIN, and CONCERTA, for CNS disorders. Seven companies have approved drugs, with Johnson & Johnson and BAUSCH among the top players.
Dopamine transporter Genetic Evidence Strong
Genetic evidence strongly supports DAT's role in diseases like dopamine transporter deficiency syndrome (score 0.85).
Strong genetic support increases confidence in DAT as a drug target and warrants investment.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
15 totalGWAS and other genetic studies link SLC6A3 to 15 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 1 strong
max H4: 0.94eQTL/pQTL signals for SLC6A3 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 Dopamine transporter Drugs
Seven companies have approved drugs targeting DAT, including Johnson & Johnson and BAUSCH.
The presence of multiple established players suggests a competitive market with moderate entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| FORFIVO XL | TWI PHARMS | 2011 | 1 |
| ADZENYS XR-ODT | NEOS THERAPS INC | 2016 | 1 |
| AUVELITY | AXSOME | 2022 | 1 |
| WELLBUTRIN SR | GSK | 1996 | 1 |
| CONCERTA | Johnson & Johnson | 2000 | 1 |
Dopamine transporter Drug Modality Landscape
Modalities
Routes of Administration
Dopamine transporter is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or gene therapies could offer differentiation.
Dopamine transporter Clinical Trials 389 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Dopamine transporter. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 118 | 99 | 7 | 12 | 93% |
| Phase 2 | 103 | 67 | 18 | 18 | 79% |
| Phase 3 | 53 | 35 | 9 | 9 | 80% |
| Phase 4 | 115 | 67 | 26 | 22 | 72% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Dopamine transporter Drug Approval Timeline (1996 - 2022)
The first drug targeting DAT was approved in 1996 (WELLBUTRIN SR), with the most recent approval in 2022 (AUVELITY).
The continued approvals indicate sustained interest, but the slowing pace suggests potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 219 (55 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 Dopamine transporter. A trial counts if an approved drug acting on Dopamine 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.