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Protein / target

Alpha-2A adrenergic receptor

Encoded byADRA2AP08913Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
47
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Alpha-1B adrenergic receptor binding

Strongest disease association

Asthma

Via encoding gene ADRA2A · Clinical evidence · score 0.62

Therapeutic position

Established drug target

Small molecules

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 overview

Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.

View complete UniProt function annotation

Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression (PubMed:2170371, PubMed:23105096, PubMed:2568356, PubMed:35245122, PubMed:27376152). Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release (PubMed:2568356, PubMed:27376152). ADRA2A and ADRA2C mediates the presynaptic feedback inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems. ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C modulates neurotransmission at lower levels of nerve activity (By similarity). The rank order of potency for agonists of ADRA2A is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol (PubMed:2170371, PubMed:2568356)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (60)

Gene Ontology

  • Caxon terminus
  • Cbasolateral plasma membrane
  • Ccytoplasm
  • Cdopaminergic synapse
  • CGABA-ergic synapse
  • Cglutamatergic synapse
  • Cneuronal cell body
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic active zone membrane
  • Creceptor complex
  • Falpha-1B adrenergic receptor binding

465 aa · 51 kDa

Biological roles

Reactome v97

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

Synaptic signallingUniProt · GOGrowth-factor signallingGOCell proliferation & survivalGOCell migrationGOG protein-coupled signallingUniProt · GOKinase signallingGO
View supporting evidence

Synaptic signalling

  • ·Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that act…
  • ·dopaminergic synapse
  • ·GABA-ergic synapse
  • ·glutamatergic synapse

Growth-factor signalling

  • ·epidermal growth factor receptor signaling pathway
  • ·positive regulation of epidermal growth factor receptor signaling pathway

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Cell migration

  • ·positive regulation of cell migration

G protein-coupled signalling

  • ·Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that act…
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor signaling pathway

Kinase signalling

  • ·protein kinase binding
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
View underlying pathways (6)

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.

GNB1GNAQGNAO1GNG2GNA12GNA13GNA11SLC6A3SLC6A2GNB3ADRA2A

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.

Approved medicines with mapped indications

3 medicines · 17 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Glaucoma2 medicines
Angioedema1 medicine
Asthma1 medicine
Depressive Disorder1 medicine
Heart Arrest1 medicine
Hemorrhage1 medicine
Hypersensitivity1 medicine
Hypertension1 medicine
Lung Diseases, Obstructive1 medicine
Migraine Disorders1 medicine
Neuralgia1 medicine
Shock, Septic1 medicine
Sinusitis1 medicine
Sleep Initiation and Maintenance Disorders1 medicine
Urticaria1 medicine
Broader indication categories (2)
Cardiovascular Diseases1 medicine
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

47 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Epinephrine
ApprovedAgonist

Adrenergic receptor agonist

Indicated for Angioedema, Asthma, Glaucoma, Heart Arrest

Acts on a complex — shared with ADRA1A, ADRB2, ADRA1D +5 more · 1 of 9 recorded protein targets — broad pharmacology

mirtazapine
ApprovedAntagonist

Adrenergic receptor alpha-2 antagonist

Indicated for Depressive Disorder, Sleep Initiation and Maintenance Disorders

Acts on a complex — shared with ADRA2C, ADRA2B · 1 of 5 recorded protein targets

clonidine
ApprovedAgonist

Adrenergic receptor alpha-2 agonist

Indicated for Glaucoma, Hypertension, Migraine Disorders, Neuralgia

Acts on a complex — shared with ADRA2C, ADRA2B · 1 of 3 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene ADRA2A

Gene-level evidence surfaced through the gene ADRA2A that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Asthma
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Attention Deficit Disorder with Hyperactivity
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Major depressive disorder
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Hypertension
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (4)
AsthmaWell supported
0.76
agreement 0.600.92
Clinical88%Literature12%

Open Targets aggregate 0.62 · 2 independent evidence families

Attention Deficit Disorder with HyperactivityWell supported
0.75
agreement 0.600.91
Clinical92%Literature8%

Open Targets aggregate 0.61 · 2 independent evidence families

Major depressive disorderWell supported
0.75
agreement 0.590.91
Clinical98%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

HypertensionModerately supported
0.74
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Asthma0.62
Attention Deficit Disorder with Hyperactivity0.61
Major depressive disorder0.61
Hypertension0.60

Drug development

57 compounds recorded · 47 approved · 8 in clinical development · 2 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
FADOLMIDINEPhase 2
GUANFACINEApproval
EPHEDRINE SULFATEApproval
HYDROXYAMPHETAMINE HYDROBROMIDEApproval
RAUWOLFIA SERPENTINAApproval
LOFEXIDINEApproval
METHYLDOPATE HYDROCHLORIDEApproval
TETRAHYDROZOLINE HYDROCHLORIDEUnknown
DEXMEDETOMIDINEApproval
ERGOTAMINE TARTRATEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

decreased body temperatureLynch et al. (2017)memory impairmentUrban et al. (2012)decreased blood pressureBowes et al. (2012)decreased noradrenaline release and sympathetic neurotransmissionBowes et al. (2012)increased gastrointestinal motilityBowes et al. (2012)increased convulsionsLynch et al. (2017)hyperglycemiaUrban et al. (2012)anesthetic-sparing effectUrban et al. (2012)sedationLynch et al. (2017)weight gainUrban et al. (2012)decreased gastric emptyingLynch et al. (2017)increased insulin secretionBowes et al. (2012)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via clonidine · NCT00262470

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2026-09-14

    Approval: EPINEPHRINE (ANDA219832)

    fda · regulatory · fda · via Epinephrine

  2. Trial status changed2026-08-28

    Effect of Adding a Low-Dose Epinephrine Bolus Prior to Infusion on Maternal Hemodynamic Stability During Cesarean Section Under Spinal Anesthesia: A Randomized Clinical Trial

    Status changed to Completed · ClinicalTrials.gov · via Epinephrine

  3. Regulatory approval2026-07-31

    Approval: EPINEPHRINE (ANDA217426)

    fda · regulatory · fda · via Epinephrine

  4. Label change2026-06-22

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  5. Product recall2026-05-14

    Recall (Class III): EPINEPHRINE

    fda · safety · fda · via Epinephrine

  6. Regulatory approval2024-08-22

    Approval: Eurneffy (EMA)

    ema · regulatory · ema · via Epinephrine

  7. New publication2023-11-07
    Impact of norepinephrine on immunity and oxidative metabolism in sepsis.

    Frontiers in immunology · 2023 · 33 citations · Europe PMC · via Epinephrine

  8. Label change2023-01-05

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  9. Supplemental approval2021-08-17

    Supplemental approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  10. New publication2019-10-31
    The effect of topical epinephrine 1:1000 with and without infiltration of 1% lidocaine with epinephrine 1:100,000 on endoscopic surgical field visualization: a double-blind randomized controlled study.

    International forum of allergy & rhinology · 2020 · 6 citations · Europe PMC · via Epinephrine

  11. Regulatory approval2013-12-18

    Approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  12. New publication2011-11-01
    Mirtazapine to reduce methamphetamine use: a randomized controlled trial.

    Archives of general psychiatry · 2011 · 115 citations · Europe PMC · via mirtazapine

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.