alpha-2 adrenergic receptor Agonists
17 drugsAbout alpha-2 adrenergic receptor
The alpha-2 adrenergic receptor (ADRA2A) modulates neurotransmitter release and is involved in various physiological processes. It is a G protein-coupled receptor that responds to catecholamines like norepinephrine and epinephrine.
Human genetics provide moderate support for ADRA2A as a therapeutic target, with variants linked to lipodystrophy (score 0.55), abnormal nasolacrimal system morphology (0.53), and type 2 diabetes (0.44). Loss-of-function variants are associated with increased risk of type 2 diabetes, suggesting activation may be beneficial.
ADRA2A is targeted by 17 FDA-approved small molecule drugs, including IGALMI, BRIMONIDINE TARTRATE AND TIMOLOL MALEATE, and ALPHAGAN P. These drugs span therapeutic areas including CNS disorders, ophthalmology, and other indications.
alpha-2 adrenergic receptor Genetic Evidence Moderate
Genetic evidence shows moderate support for ADRA2A, with a max score of 0.55 linking it to lipodystrophy.
Further investigation of ADRA2A's role in lipodystrophy could reveal novel therapeutic opportunities.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in endocrine system disease, nutritional or metabolic disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
3 totalGWAS and other genetic studies link ADRA2A to 3 diseases.
🔗 Colocalization Evidence 3 strong
max H4: 0.95eQTL/pQTL signals for ADRA2A 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 alpha-2 adrenergic receptor Drugs
Fourteen companies have approved drugs targeting ADRA2A, with Novartis and Fresenius Kabi among the top players.
The fragmented competitive landscape suggests relatively low barriers to entry for new ADRA2A-targeting drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| BRIMONIDINE TARTRATE | ALEMBIC | 2003 | 2 |
| BRIMONIDINE TARTRATE AND TIMOLOL MALEATE | SABA ILAC SANAYIVE | 2022 | 2 |
| SIMBRINZA | Novartis | 2013 | 2 |
| DEXMEDETOMIDINE HYDROCHLORIDE | Teva | 2014 | 1 |
| ONTRALFY | FIDELITY BIOPHARMA | 2024 | 1 |
| REMERON SOLTAB | Merck | 2001 | 1 |
| LOFEXIDINE HYDROCHLORIDE | MSN | 2024 | 1 |
| RYZUMVI | FAMYGEN LIFE SCI | 2023 | 1 |
| ONYDA XR | TRIS PHARMA INC | 2024 | 1 |
| ZANAFLEX | LEGACY | 1996 | 1 |
| REMERON | Merck | 1996 | 1 |
| MIRVASO | GALDERMA LABS LP | 2013 | 1 |
| PRECEDEX | Pfizer | 1999 | 1 |
| LUCEMYRA | BIOCORRX PHARMS | 2018 | 1 |
alpha-2 adrenergic receptor Drug Modality Landscape
Modalities
Routes of Administration
alpha-2 adrenergic receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage.
alpha-2 adrenergic receptor Clinical Trials 817 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on alpha-2 adrenergic receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 83 | 53 | 16 | 14 | 77% |
| Phase 2 | 170 | 116 | 26 | 27 | 82% |
| Phase 3 | 147 | 98 | 20 | 29 | 83% |
| Phase 4 | 417 | 298 | 45 | 73 | 87% |
Top Sponsors
By Modality
Top Conditions
alpha-2 adrenergic receptor Drug Approval Timeline (1996 - 2024)
The first ADRA2A-targeting drug was approved in 1996 (REMERON), with the most recent approval in 2024 (ONYDA XR).
The continued approval of new drugs indicates sustained interest and potential for further development in this area.
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Deep insights for drug target analysis
Competitive Landscape
- • 15 companies competing
- • Market share by company
Full Drug Portfolio
- • All 17 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 17-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 421 (41 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 alpha-2 adrenergic receptor. A trial counts if an approved drug acting on alpha-2 adrenergic receptor 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.