ADRA2A adrenoceptor alpha 2A
ENSG00000150594 · protein coding · Open Targets profile
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). {ECO:0000250|UniProtKB:Q01338, ECO:0000269|PubMed:2170371, ECO:0000269|PubMed:23105096, ECO:0000269|PubMed:2568356, ECO:0000269|PubMed:27376152, ECO:0000269|PubMed:35245122}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 1.0120999813079834 (upper bound 1.9976999759674072). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 180 registry trials, updated in the last three years, of the most advanced drugs against ADRA2A (ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Chatkaew PongmalaUniversity of Michigan · 2 of 2 trials Phase 2+
- Andre Telis AraujoFederal University of Paraíba · 1 of 1 trials Phase 2+
- Ari DjatikusumoDepartment of Ophthalmology, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital, Indonesia · 1 of 1 trials Phase 2+
- Ban L SngKK Women's and Children's Hospital · 1 of 1 trials Phase 2+
- Ban Leong SngKK Women's and Children's Hospital · 1 of 1 trials Phase 2+
- Cecilia BergeriaJohns Hopkins University · 1 of 1 trials Phase 2+
- Charlotte BAUDUniversity Hospital, Clermont-Ferrand · 1 of 1 trials Phase 2+
- Chris CarlstenUniversity of British Columbia · 1 of 1 trials Phase 2+
- Christopher D. VerricoBaylor College of Medicine · 1 of 1 trials Phase 2+
- Cristiano SconzaHumanitas Clinical and Research Center · 1 of 1 trials Phase 2+
- Dong-Xin WangPeking University First Hospital · 1 of 1 trials Phase 2+
- Emmanuel FUTIERUniversity Hospital, Clermont-Ferrand · 1 of 1 trials Phase 2+
- Eric StrainJohns Hopkins University · 1 of 1 trials Phase 2+
- Ernest ChoyAcademic Dept of Rheumatology Kings College London · 1 of 1 trials Phase 2+
- Eun-Hee KimSeoul National University Hospital · 1 of 1 trials Phase 2+
Registry trials of ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidine updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 168 of 171 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 9 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
46 trials of drugs against ADRA2A were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidine, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 46.
- terminated · 2026-10-28 · Algemeen Ziekenhuis Maria Middelares · matched by the registry's drug synonyms“The planned interim analysis revealed greater variability than expected, requiring a larger sample size. Given the limited eligible population, recruitment was deemed infeasible within a reasonable timeframe, leading to study termination.”
- withdrawn · 2026-10-28 · Aarhus University Hospital · matched by the registry's drug synonymsNo reason given
- withdrawn · 2026-09-21 · University Ghent · matched by the registry's drug synonyms“the campaign section has not yet been finalised. A preliminary evaluation is difficult in this case, as the impact stems primarily from a media campaign and PR initiatives. Such effects are harder to assess in advance. Consequently, this specific stu”
- withdrawn · 2026-03-19 · Centre hospitalier de l'Université de Montréal (CHUM) · matched by the registry's drug synonyms“The study was withdrawn prior to participant enrollment.”
- terminated · 2025-12-11 · Hopital Charles Nicolle · Ephedrine (6 mg boluses)“the investigators collected the necessary sample size for the internal validity of the study”
- withdrawn · 2025-09-16 · Alcon Research · matched by the registry's drug synonyms“Management decision”
- withdrawn · 2025-08-01 · USWM, LLC (dba US WorldMeds) · LUCEMYRA (lofexidine) tablets“Study withdrawn prior to enrollment due to strategic portfolio decisions following divestiture of the investigational product.”
- withdrawn · 2025-07-23 · Walter Reed Army Medical Center · matched by the registry's drug synonyms“Lack of resources and not because of any concern with the safety or effectiveness of the procedures studied.”
- terminated · 2024-10-21 · USWM, LLC (dba US WorldMeds) · Lofexidine“COVID pandemic and enrollment issues necessitating an adjustment to the study design.”
- terminated · 2024-06-03 · Asociación para Evitar la Ceguera en México · matched by the registry's drug synonyms“Poor accrual”
- terminated · 2024-05-30 · Asociación para Evitar la Ceguera en México · matched by the registry's drug synonyms“Undefined”
- terminated · 2023-12-08 · University of Toronto · matched by the registry's drug synonyms“The study was terminated because of low recruitment/enrolment due to multiple reasons, including 1) Elderly population, often with other health issues, thus not being able to commit to all of the follow-up appointments and 2) COVID-19 restrictions.”
- terminated · 2023-05-22 · New York State Psychiatric Institute · matched by the registry's drug synonyms“The project end date was reached prior to the full sample enrollment”
- withdrawn · 2022-10-31 · Azidus Brasil · Loratadine + Pseudoephedrine sulfateNo reason given
- suspended · 2022-10-17 · Jessica M D'Amico · matched by the registry's drug synonyms“PI left UofL and intends to reopen study at University of Alberta”
- suspended · 2022-07-22 · Beijing Chao Yang Hospital · matched by the registry's drug synonyms“There are difficulties in recruiting patients”
- terminated · 2022-07-05 · University Hospitals Cleveland Medical Center · matched by the registry's drug synonyms“Funding”
- withdrawn · 2022-05-24 · YingHsuanTai · matched by the registry's drug synonyms“COVID outbreak in the community”
- terminated · 2022-04-18 · Shahid Beheshti University · matched by the registry's drug synonymsNo reason given
- withdrawn · 2021-10-28 · National Institute of Allergy and Infectious Diseases (NIAID) · Pseudoephedrine hydrochlorideNo reason given
- withdrawn · 2021-07-29 · University of Miami · matched by the registry's drug synonyms“Withdrawn as more data drug analysis is recommended before the study.”
- terminated · 2021-05-27 · Shire · matched by the registry's drug synonymsNo reason given
- terminated · 2021-05-05 · Vanderbilt University · Pseudoephedrine + 480 ml water, Pseudoephedrine + 50 ml water“funding terminated”
- terminated · 2020-10-14 · Duke University · Ephedrine“Significant challenges recruiting a difficult patient population with most surgeries occurring out of hours”
- withdrawn · 2020-06-30 · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · matched by the registry's drug synonyms“Study not begun due to continued laboratory work on the feasibility of outcome measures.”
Paediatric incentives and obligations for ADRA2A's drugs
For ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidine: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · ADRA2A is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-003387-PIP01-22 (xylometazoline hydrochloride;sodium hyaluronate, Treatment of acute rhinosinusitis): W: decision granting a waiver in all age groups for all conditions or indications, 14 Jun 2023Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-003387-PIP01-22, 2026-11-11
- EU orphan designation: yes · EU/3/23/2764 positive 20 Mar 2023: Treatment of vanishing white matter disease; EU/3/09/625 positive 29 Apr 2009: Treatment of traumatic spinal cord injuryRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidineRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidineRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 64 interventional studies of ephedrine, hydroxyamphetamine hydrobromide, rauwolfia serpentina, methyldopate, guanabenz, ergoloid mesylates, xylometazoline, naphazoline, dipivefrin, alseroxylon, tolazoline, lofexidine include patients under 18; 6 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 57 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.