Protein / target

Alpha-2C adrenergic receptor

ADRA2CP18825Homo sapiensSwiss-Prot
UniProt: P18825Ensembl: ENSG00000184160HGNC: HGNC:283NCBI Gene: 152
Clinically validated
Therapeutic maturity
47
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Alpha-2A adrenergic receptor binding

Primary system

Nervous system

Strongest disease association

major depressive disorder

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

47 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

47 approved · 9 in clinical development

30 linked trials

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

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:2842764). Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release (PubMed:2842764). 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 physiological agonists of ADRA2C is epinephrine > norepinephrine > dopamine (PubMed:2842764)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (22)

Gene Ontology

  • Ccytoplasm
  • Cendosome
  • Cplasma membrane
  • Falpha-2A adrenergic receptor binding
  • Falpha2-adrenergic receptor activity
  • Fepinephrine binding
  • Fprotein heterodimerization activity
  • Fprotein homodimerization activity
  • Padenylate cyclase-inhibiting adrenergic receptor signaling pathway
  • Padrenergic receptor signaling pathway
  • Pcell-cell signaling
  • Pepidermal growth factor receptor signaling pathway

462 aa · 50 kDa

Biological roles

Reactome v97

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

G protein-coupled signallingUniProt · GOSynaptic signallingUniProtKinase signallingGOMuscle contractionGOHaemostasisGO
View supporting evidence

G protein-coupled signalling

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

Synaptic signalling

  • ·Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that act…

Kinase signalling

  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Muscle contraction

  • ·regulation of smooth muscle contraction

Haemostasis

  • ·platelet activation
View underlying pathways (6)
Adrenoceptors
Adrenaline signalling through Alpha-2 adrenergic receptor
Adrenaline,noradrenaline inhibits insulin secretion
G alpha (i) signalling events
G alpha (z) signalling events
Surfactant metabolism

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.

GNAQGNA11GNA12GNA13SLC6A3ADRA2AAGTSLC6A2GNB3YES1ADRA2C

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Epinephrine
ApprovedAgonist

Adrenergic receptor agonist

Appears in clinical studies involving sudden cardiac arrest, asthma, sinusitis, septic shock

Acts on a complex — shared with ADRA1A, ADRA2A, ADRB2 +5 more · 1 of 9 recorded protein targets — broad pharmacology

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

major depressive disorder0.99

Clinical · overall 0.61

ocular hypertension0.99

Clinical · overall 0.60

attention deficit-hyperactivity disorder0.98

Clinical · overall 0.60

hypertensive disorder0.98

Clinical · overall 0.60

Nasal congestion0.98

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

open-angle glaucoma0.60

Clinical

glaucoma0.60

Clinical

asthma0.60

Clinical

seasonal allergic rhinitis0.59

Clinical

Pain0.59

Clinical

Show all associations
major depressive disorder0.61
attention deficit-hyperactivity disorder0.60
ocular hypertension0.60
hypertensive disorder0.60
Nasal congestion0.60
open-angle glaucoma0.60
glaucoma0.60
asthma0.60
seasonal allergic rhinitis0.59
Pain0.59

Open Targets ranks 396 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 58 total

APRACLONIDINEApproval

glaucoma · ptosis

DIPIVEFRINApproval

glaucoma

EPHEDRINE HYDROCHLORIDEApproval

Nasal congestion · seasonal allergic rhinitis · common cold

LABETALOLApproval

cardiovascular disorder · Hypertension · preeclampsia

LEVONORDEFRINUnknown

Pain

ERGOTAMINEApproval

Headache · migraine disorder · orthostatic hypotension

ERGOLOID MESYLATESApproval

cardiovascular disorder · vascular dementia · fragile X syndrome

HYDROXYAMPHETAMINE HYDROBROMIDEApproval

Horner syndrome

LOFEXIDINEApproval

opiate dependence · drug dependence · cannabis dependence

METHYLDOPATE HYDROCHLORIDEApproval

Hypertension

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Approved Drug

Safety liabilities

stress responsevenous contraction (contraction of human saphenous vein)receptor bindingstartle reflexhypertensionlocomotioncardiac ischemia

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.

Management of Acute Pulmonary Hypertensive Crisis in Children With Known Pulmonary Arterial HypertensionPHASE4

COMPLETED · via Epinephrine · NCT05439460

Nebulized Epinephrine Versus Nebulized Salbutamol in Bronchiolitis Among Children Aged 1month-24monthsNA

COMPLETED · via Epinephrine · NCT03814954

Effect of Preventive Medicine on the Postreperfusion SyndromeNA

COMPLETED · via Epinephrine · NCT01080625

Effect of Push-Dose Adrenaline on Peri-intubation Cardiovascular and Clinical Outcomes During Rapid Sequence Intubation in the Emergency Department: A Prospective, Randomized, Double-Blind, Placebo-Controlled TrialPHASE4

NOT_YET_RECRUITING · via Epinephrine · NCT07620327

Efficacy of Multimodal Peri- and Intraarticular Drug Injections in Total Knee ArthroplastyPHASE4

COMPLETED · via Epinephrine · NCT00562627

Can the Risk of RD and Hypoglycemia in Children Born at Elective CS be Reduced by Injection of AdrenalineNA

COMPLETED · via Epinephrine · NCT00322660

Show remaining trials (24)
Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK TrialPHASE2

TERMINATED · via Epinephrine · NCT00401882

Comparison of Absorption of Epinephrine Into the Circulation After Epinephrine Intranasal Spray Administration and After Intramuscular InjectionNA

COMPLETED · via Epinephrine · NCT01432522

A Randomized Clinical Trial to Compare the Addition of Epinephrine (no Epinephrine, 100mcg, and 200mcg) to the Standard Dose of Hyperbaric Bupivacaine 12mg, Fentanyl 20mcg and Morphine 150mcg in Scheduled C-sections.PHASE4

WITHDRAWN · via Epinephrine · NCT03335293

Hemostatic and Hemodynamic Effects of Intranasal Injection Compared to Topical Administration of Epinephrin in Endoscopic Sinus SurgeryNA

UNKNOWN · via Epinephrine · NCT01075581

Multicenter Randomized Controlled Trial of Gastric Endoscopic Submucosal Dissection With or Without Epineprhine Added SolutionPHASE3

COMPLETED · via Epinephrine · NCT04032119

Comparing Blood Loss and Visualization After the Preoperative Use of Topical 0.05% Oxymetazoline Versus 1:1000 Epinephrine Prior to Endoscopic Sinus SurgeryPHASE4

COMPLETED · via Epinephrine · NCT03228914

Local Effects of Epinephrine on Lactate, Glucose, Lipid and Protein Metabolism in Bilaterally Perfused Human LegsNA

COMPLETED · via Epinephrine · NCT01116609

Over-the-scope Clips and Standard Treatments in Endoscopic Control of of Acute Bleeding From Non-variceal Upper GI Causes(OTSC Study)NA

COMPLETED · via Epinephrine · NCT03216395

Hemodynamic Stability of Bupivacaine With and Without Adrenaline for Paracervical Block for Cervical Conization During General Anesthesia: A Randomized Controlled Double Blinded StudyPHASE4

COMPLETED · via Epinephrine · NCT02368054

Ultrasound Guided Motor Sparing Knee Blocks With or Without Dexmedetomidine for Postoperative Analgesia Following Knee Arthroplasty: a Randomized Double Blinded StudyPHASE3

UNKNOWN · via Epinephrine · NCT02540070

Role of Low Dose Epinephrine Boluses For Acute Hypotension in The Pediatrics ICUNA

UNKNOWN · via Epinephrine · NCT03671070

A Phase 1 Comparative Bioavailability Study of Inhaled Epinephrine and Intramuscular Epinephrine Administered to Healthy AdultsPHASE1

COMPLETED · via Epinephrine · NCT05152901

Efficacy and Safety of Periarticular Multimodal Drug Injections in Total Knee ArthroplastyPHASE4

COMPLETED · via Epinephrine · NCT00901628

Efficacy of Lidocaine Saline Irrigation in Patients Undergoing Shoulder Arthroscopy: Randomized Controlled StudyNA

COMPLETED · via Epinephrine · NCT05624957

4% Articaine and 2% Lidocaine by Intraligamentary Technique in Irreversible PulpitisPHASE3

COMPLETED · via Epinephrine · NCT02807298

Transversus Abdominis Plane (TAP) Infiltration vs. Surgical Infiltration of Local Anesthetic in Laparoscopic and Robotic Assisted HysterectomyPHASE4

COMPLETED · via Epinephrine · NCT02519023

The Effect of The Serratus Block on Analgesia After Breast Surgery A Randomized Controlled Double-Blinded StudyPHASE2/PHASE3

COMPLETED · via Epinephrine · NCT02453516

Endoscopic Injection of Autologous Blood Versus Diluted Epinephrine for Control of Actively Bleeding Gastroduodenal UlcersNA

COMPLETED · via Epinephrine · NCT01560702

Perioperative Analgesic Management Using Conventional Versus Regional Nerve Block in Craniotomy Surgeries in Lower Middle-Income Class CountriesPHASE4

COMPLETED · via Epinephrine · NCT07425678

Liposomal Bupivacaine Versus Bupivacaine for Postoperative Analgesia Following Video-assisted Thoracoscopic Surgery.PHASE2/PHASE3

UNKNOWN · via Epinephrine · NCT03036085

Optimal Timing of Intercostal Nerve Blocks During Video-Assisted Thoracic SurgeriesPHASE4

COMPLETED · via Epinephrine · NCT02980835

A Phase I Study of Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and LymphomasPHASE1

COMPLETED · via Epinephrine · NCT03030417

Role of Catheter Administered Intracoronary Epinephrine in Prevention of No-Reflow in STEMI Patients Undergoing Primary Percutaneous Coronary InterventionPHASE3

RECRUITING · via Epinephrine · NCT06847568

Comparison of Opioid-based Anesthesia, Opioid-free Anesthesia Based on Intravenous Drugs and Opioid-free Anesthesia With Thoracic Paravertebral Block, in Patients Undergoing Laparoscopic Gastric Bypass Surgery for ObesityNA

NOT_YET_RECRUITING · via Epinephrine · NCT07084753

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

major depressive disorderModerately supported
0.75
agreement 0.59–0.90
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

attention deficit-hyperactivity disorderModerately supported
0.74
agreement 0.59–0.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

ocular hypertensionModerately supported
0.74
agreement 0.57–0.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

hypertensive disorderModerately supported
0.74
agreement 0.58–0.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Nasal congestionModerately supported
0.74
agreement 0.57–0.90
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

12

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-06-22

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  2. Product recall2026-05-14

    Recall (Class III): EPINEPHRINE

    fda · safety · fda · via Epinephrine

  3. Regulatory approval2024-08-22

    Approval: Eurneffy (EMA)

    ema · regulatory · ema · via Epinephrine

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

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

  5. Label change2023-01-05

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  6. Supplemental approval2021-08-17

    Supplemental approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  7. 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

  8. Indication expanded2019-01-29

    Indication expansion: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  9. Label change2017-08-09

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  10. Label change2016-05-18

    Label change: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  11. Supplemental approval2015-12-23

    Supplemental approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

  12. Regulatory approval2013-12-18

    Approval: EPINEPHRINE (NDA204640)

    fda · regulatory · fda · via Epinephrine

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.