ADRA1A adrenoceptor alpha 1A
ENSG00000120907 · protein coding · Open Targets profile
Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C (PubMed:37563160). ADRA1A binds the catecholamine ligands norepinephrine and epinephrine (PubMed:18802028, PubMed:37563160, PubMed:7815325, PubMed:8024574, PubMed:8183249, PubMed:8832064). Can also couple to G(14) protein (By similarity). Nuclear ADRA1A forms heterooligomers with ADRA1B to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes (PubMed:18802028, PubMed:22120526). At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy (PubMed:24567387). Additionally, functions as a vasopressor in resistance arteries and plays a role in maintaining normal arterial blood pressure (By similarity). {ECO:0000250|UniProtKB:P18130, ECO:0000250|UniProtKB:P97718, ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526, ECO:0000269|PubMed:24567387, ECO:0000269|PubMed:37563160, ECO:0000269|PubMed:7815325, ECO:0000269|PubMed:8024574, ECO:0000269|PubMed:8183249, ECO:0000269|PubMed:8832064}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 1.0477999448776245 (upper bound 1.4141000509262085). 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 255 registry trials, updated in the last three years, of the most advanced drugs against ADRA1A (phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Jill BarnesUW Madison · 2 of 2 trials Phase 2+
- Shiv Kumar SarinInstitute of Liver & Biliary Sciences · 2 of 2 trials Phase 2+
- Sean van DiepenUniversity of Alberta · 1 of 2 trials Phase 2+
- A A. FrankenIsala · 1 of 1 trials Phase 2+
- Ahlem TrifiHopital La Rabta · 1 of 1 trials Phase 2+
- Alain PuechKinnov Therapeutics · 1 of 1 trials Phase 2+
- Alexander ZarbockUniversity Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy · 1 of 1 trials Phase 2+
- Anne RichardsSan Francisco Veterans Affairs Medical Center · 1 of 1 trials Phase 2+
- Arafa GomaaHelwan University · 1 of 1 trials Phase 2+
- B. S SegalAdvocate Health-Wake Forest School of Medicine · 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+
- Bas HavekesMaastricht University Medical Center · 1 of 1 trials Phase 2+
- Bruno LaviolleRennes University Hospital · 1 of 1 trials Phase 2+
- C B. BrouwerCanisius-Wilhelmina Hospital · 1 of 1 trials Phase 2+
Registry trials of phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramine 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; 236 of 240 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. 15 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
62 trials of drugs against ADRA1A were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramine, 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 62.
- 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.”
- terminated · 2026-10-14 · Yale University · matched by the registry's drug synonyms“The study was terminated prematurely due to lack of continued funding.”
- suspended · 2026-10-09 · Ergun Y. Uc · Terazosin 5 MG“Study not funded”
- withdrawn · 2026-10-07 · Nandakumar Narayanan · Terazosin Hydrochloride“Not Funded”
- 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”
- 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”
- suspended · 2025-08-13 · Charite University, Berlin, Germany · Doxazosin“Early termination due to recruitment issues”
- withdrawn · 2025-05-23 · University of Colorado, Denver · Prazosin“COVID recruitment issues”
- terminated · 2024-11-26 · University of Maryland, Baltimore · matched by the registry's drug synonyms“Due to the extended COVID-19 shutdown, the study was terminated early with a smaller sample size of 12 included in the analyses”
- terminated · 2024-02-26 · VA Office of Research and Development · prazosin hydrochloride“staffing issues and COVID”
- terminated · 2024-01-23 · Otsuka Pharmaceutical Development & Commercialization, Inc. · Prazosin“The decision to terminate the trial early was not based on safety concerns. The trial was terminated early due to some implausible blood pressure values being captured, which was the primary endpoint of the study.”
- suspended · 2023-11-18 · Rennes University Hospital · matched by the registry's drug synonyms“study suspended until new therapeutic units are available”
- terminated · 2023-04-10 · Johns Hopkins University · Prazosin“Lack of recruitment”
- withdrawn · 2023-04-04 · Montreal Heart Institute · matched by the registry's drug synonyms“Not enough patients”
- suspended · 2022-11-02 · University of Manitoba · Prazosin“COVID-19”
- withdrawn · 2022-10-31 · Azidus Brasil · Loratadine + Pseudoephedrine sulfateNo reason given
- withdrawn · 2022-09-01 · The University of Texas Health Science Center, Houston · Doxazosin XL“No funding”
- 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”
- withdrawn · 2021-11-16 · University of California, Berkeley · 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
- terminated · 2021-10-07 · Kimberly S Jones · Dihydroergotamine (DHE)“Difficulty recruiting participants”
- terminated · 2021-05-05 · Vanderbilt University · Pseudoephedrine + 480 ml water, Pseudoephedrine + 50 ml water“funding terminated”
- terminated · 2021-04-12 · New York State Psychiatric Institute · matched by the registry's drug synonyms“Study terminated by sponsor due to bad risk/benefit ratio.”
Paediatric incentives and obligations for ADRA1A's drugs
For phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramine: 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 · ADRA1A 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 2023; EMEA-003380-PIP01-22 (Finasteride;doxazosin (mesylate), Treatment of benign prostatic hyperplasia): W: decision granting a waiver in all age groups for all conditions or indications, date not givenRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramineRule: 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 phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramineRule: 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 phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramineRule: 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 · 71 interventional studies of phentolamine, naphazoline, xylometazoline, mephentermine, ephedrine, norepinephrine bitartrate, ergotamine, hydroxyamphetamine hydrobromide, doxazosin, terazosin, prazosin, trimipramine include patients under 18; 11 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 66 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.