Adrenomedullin
A blood-pressure-lowering hormone discovered in 1993, infused in small trials for pulmonary hypertension, ulcerative colitis and Crohn's disease
Adrenomedullin is a 52-amino-acid peptide hormone first isolated in 1993 from a human adrenal tumour and named for the adrenal medulla, where it is abundant. It widens blood vessels and has been given by infusion in small trials for pulmonary hypertension, ulcerative colitis and Crohn's disease. It is not approved as a medicine in the US.
What is it?
Adrenomedullin was found in 1993 by tracking a substance that raised cyclic AMP in platelets. It produced a potent, long-lasting fall in blood pressure, circulated in blood in considerable amounts and resembled calcitonin gene-related peptide slightly, which suggested a new hormone in blood-pressure control. Its levels rise sharply in severe inflammation such as sepsis, which has made it of interest as a blood marker.
As a drug it has a handicap: it lasts under 30 minutes in the bloodstream, so it has to be infused. In a 2000 study of 13 people with pulmonary hypertension, an infusion raised cardiac output by 44% and cut pulmonary vascular resistance by 32%, while systemic blood pressure fell. A 2022 review notes that early human studies in heart failure, heart attack, pulmonary hypertension and peripheral artery disease did not succeed.
Japanese researchers then turned to inflammatory bowel disease, with doses chosen to limit the fall in blood pressure. In 28 patients with steroid-resistant ulcerative colitis, no dose beat placebo at two weeks, though the highest did better at eight weeks; in 24 patients with Crohn's disease resistant to biologic drugs, the primary end point was missed and a difference appeared only at 24 weeks.
The newer trials have not changed that record. A 60-patient stroke trial and a 64-patient COVID-19 pneumonia trial both found the infusion safe and no better than placebo. A phase 1 study in healthy men tested rates up to 15 ng/kg/min, the rate later used in the COVID-19 trial, and an infusion in people with migraine triggered attacks in 55% against 15% on placebo. A PEGylated, longer-lasting version has so far been tested in mice.
A second approach targets the hormone with antibodies rather than giving it. Adrecizumab and enibarcimab bind adrenomedullin without blocking it and raise its level in blood; in septic shock and acute heart failure they were well tolerated, without a clear benefit yet. Meanwhile, blood levels have become a prognostic marker: across 18,110 heart failure patients, higher MR-proADM and bio-ADM predicted death, and similar links appear in heart attack, amyloidosis, sepsis and infant bronchiolitis.
Mechanism of Action
Adrenomedullin is a peptide hormone that slightly resembles calcitonin gene-related peptide; it widens blood vessels and raises cyclic AMP, including through the AM1 receptor (CLR with RAMP2).
Vasodilation
It lowers blood pressure and pulmonary vascular resistance, which is both its therapeutic idea and its dose-limiting effect.
cAMP signalling
It raises cyclic AMP through the AM1 receptor (CLR with RAMP2), the same signal used to measure the PEGylated version.
A blood marker
Levels rise in sepsis, heart failure and other severe illness, and MR-proADM and bio-ADM are studied as prognostic tests.
Published Research
These are the studies that describe adrenomedullin, read from their PubMed abstracts: three human trials, its discovery and a review of its translation.
Steroid-resistant ulcerative colitis: 28 patients
Infusions of 5, 10 or 15 ng/kg/min for 8 hours a day over 14 days did not beat placebo on the Mayo score at 2 weeks. At 8 weeks the highest dose scored better (-9.3 vs -3.0), with remission in all 3 of its assessed patients against 0 of 2. Adverse events were mild.
Biologic-resistant Crohn's disease: 24 patients
Infusions of 10 or 15 ng/kg/min for 8 hours a day over 7 days missed the primary end point at 8 weeks. Disease activity stayed lower through 24 weeks while the placebo group's improvement faded, a difference significant only at 24 weeks. Adverse events were mild.
Pulmonary hypertension: 13 patients
An infusion of 0.05 µg/kg/min raised cardiac index by 44% and cut pulmonary vascular resistance by 32%; systemic blood pressure fell, heart rate rose and aldosterone fell. Nothing changed on placebo.
Phase 1 in healthy men
Healthy men received placebo or 3, 9 or 15 ng/kg/min as a 12-hour infusion, or 15 ng/kg/min for 8 hours a day for 7 days. There were no serious adverse events and blood pressure held; levels fell back to baseline after stopping, with a half-life under 60 minutes, and one man withdrew with headache.
AMFIS: acute ischaemic stroke
In a phase 2 trial of 60 patients with non-severe, non-embolic ischaemic stroke, adrenomedullin caused no intervention-related serious adverse events, but the change in stroke score by day 7 was no better than placebo (−0.76 against −1.08).
COVID-19 pneumonia
In a placebo-controlled phase 2a trial in Japan of 33 patients with severe and 31 with moderate COVID-19 pneumonia, a 15 ng/kg/min infusion did not shorten ventilation or oxygen support or improve 30-day clinical status; mild vasodilatory side effects occurred.
Heart attack pilot
In 10 patients with a first heart attack, a 12-hour infusion started before reperfusion kept haemodynamics stable in 8; wall motion in the infarct area improved and infarct size on MRI was smaller at 3 months than at baseline, with no control group.
It can trigger migraine
In a randomised crossover study of 20 people with migraine without aura, 55% had a migraine-like attack after an adrenomedullin infusion against 15% after placebo; flushing, heat sensation and palpitations were common.
AdrenOSS-2: an antibody in septic shock
In septic shock patients with high bio-adrenomedullin, the non-neutralising antibody adrecizumab was well tolerated; the sepsis support index did not differ from placebo and 28-day mortality was 23.9% against 27.7%, not significant.
ADESTE: an antibody in heart failure
In a pilot safety study in acute heart failure, enibarcimab infusions raised circulating bio-adrenomedullin and lowered blood pressure at the higher dose without severe hypotension or treatment-related serious adverse events.
Cardiogenic shock after ACS
In initially stable patients with acute coronary syndromes, ADM-Gly and bio-ADM independently predicted in-hospital cardiogenic shock and 1-year mortality, and improved an existing risk score in external validation.
Cardiac amyloidosis
In a multicentre study, bio-ADM above 29 pg/mL predicted death and major cardiac events and improved two staging systems for transthyretin cardiac amyloidosis, but not for light-chain amyloidosis.
Sepsis and the microcirculation
In ICU sepsis patients, higher MR-proADM was modestly linked to poorer microvascular perfusion, and rising levels tracked worsening perfusion; it predicted need for dialysis but not mortality.
Infant bronchiolitis
Plasma MR-proADM independently predicted longer hospital stay, bacterial coinfection and need for respiratory, fluid and inotropic support in infants with bronchiolitis.
The discovery
Isolated from a human pheochromocytoma: 52 amino acids, one disulfide bond, slight homology with CGRP. It caused a potent, long-lasting fall in blood pressure and circulated in blood, suggesting a new blood-pressure hormone.
From heart disease to the gut
Adrenomedullin rises sharply in sepsis and lasts under 30 minutes in blood. Early human studies in heart failure, heart attack, pulmonary hypertension and peripheral artery disease did not succeed; the authors developed it for bowel disease and long-acting derivatives.
A marker in acute heart failure
Across 21 studies of 18,110 patients, MR-proADM and bio-ADM at admission or discharge were each associated with higher risk of death and major cardiac events, with hazard ratios of 1.17 to 2.72.
Stroke meta-analysis
Bio-ADM was raised in ischaemic and haemorrhagic stroke and higher in patients who died, but it did not independently predict death after adjustment (pooled odds ratio 1.11).
A PEGylated version for colitis
A 40 kDa PEGylated adrenomedullin was more stable in plasma than the native peptide, and a single intravenous dose as low as 25 nmol/kg treated and prevented colitis in mice.
Dosing Data
There is no approved product. Trials infused it intravenously at up to 15 ng/kg/min, because it is cleared from blood within an hour.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the human trials above.
Contraindications & Cautions
Adrenomedullin has no label. These cautions follow from its effects and its trial record.
Legal Status
Adrenomedullin is a research compound; no US application covers it.
Frequently Asked Questions
?What is adrenomedullin?
A 52-amino-acid hormone, discovered in 1993, that widens blood vessels and lowers blood pressure.
?Is adrenomedullin a treatment for anything?
Not an approved one. Small Japanese trials in ulcerative colitis and Crohn's disease missed their main end points, with later differences that need confirming.
?Why is it given by infusion?
It lasts under 30 minutes in the bloodstream, so trials infused it for hours a day; longer-acting derivatives are being developed.
?What were the side effects?
Mild effects of widened blood vessels, such as lower blood pressure and a faster heart rate.
?Did adrenomedullin work for stroke or COVID-19?
No. In a 60-patient phase 2 trial in ischaemic stroke and a 64-patient trial in COVID-19 pneumonia, infusions were well tolerated but no better than placebo on the main measures.
?What is bio-ADM?
It is the measurable active form of adrenomedullin in blood. Higher bio-ADM or MR-proADM levels predicted death in a meta-analysis of 18,110 heart failure patients, and are studied in heart attack, amyloidosis, stroke and sepsis.
References
- [fda] FDA. Drugs@FDA (openFDA): no application for adrenomedullin. Read September 30, 2026.
- [pubmed] Kita T, et al. "Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial." J Gastroenterol, 2021;56(2):147-157. PMID: 33140199.
- [pubmed] Kita T, et al. "Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial." J Gastroenterol Hepatol, 2022;37(11):2051-2059. PMID: 35840351.
- [pubmed] Nagaya N, et al. "Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension." Heart, 2000;84(6):653-8. PMID: 11083748.
- [pubmed] Kitamura K, et al. "Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma." Biochem Biophys Res Commun, 1993;192(2):553-60. PMID: 8387282.
- [pubmed] Kita T, et al. "Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases." Hypertens Res, 2022;45(3):389-400. PMID: 34992239.
- [pubmed] Geven C, et al. "Adrenomedullin and Adrenomedullin-Targeted Therapy As Treatment Strategies Relevant for Sepsis." Front Immunol, 2018;9:292. PMID: 29520277.
- [pubmed] Meeran K, et al. "Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study." J Clin Endocrinol Metab, 1997;82(1):95-100. PMID: 8989240.
- [pubmed] Kita T, et al. "Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial." Drug Des Devel Ther, 2020;14:1-11. PMID: 32021087.
- [pubmed] Yoshimoto T, et al. "Efficacy and safety of adrenomedullin for acute ischemic stroke (AMFIS): a phase 2, randomized, double-blinded, placebo-controlled, clinical trial." EClinicalMedicine, 2024;77:102901. PMID: 39618942.
- [pubmed] Kita T, et al. "Adrenomedullin Therapy for Moderate-to-Severe COVID-19 Pneumonia: Double-Blind Placebo-Controlled Phase 2a Trial." Viruses, 2025;17(7). PMID: 40733599.
- [pubmed] Kataoka Y, et al. "The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction." J Cardiovasc Pharmacol, 2010;56(4):413-9. PMID: 20930593.
- [pubmed] Ghanizada H, et al. "Effect of Adrenomedullin on Migraine-Like Attacks in Patients With Migraine: A Randomized Crossover Study." Neurology, 2021;96(20):e2488-e2499. PMID: 33827963.
- [pubmed] Laterre PF, et al. "Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial." Intensive Care Med, 2021;47(11):1284-1294. PMID: 34605947.
- [pubmed] Hartopo AB, et al. "The ADESTE trial: A phase 2 study of enibarcimab, a monoclonal antibody targeting adrenomedullin, in acute heart failure." ESC Heart Fail, 2025;12(3):1848-1860. PMID: 39809577.
- [pubmed] Huang W, et al. "Role of Adrenomedullin as a Prognostic Biomarker in Acute Heart Failure Patients: A Systematic Review and Meta-Analysis." Cardiology, 2026:1-17. PMID: 41569961.
- [pubmed] Wang Y, et al. "Adrenomedullin system dysregulation predicts cardiogenic shock and mortality in acute coronary syndromes." Eur Heart J, 2026. PMID: 42668424.
- [pubmed] Müller ML, et al. "Bio-Adrenomedullin Predicts Death and Major Adverse Cardiovascular Events in Cardiac Amyloidosis: A Cross-Continental Multicenter Study." J Am Heart Assoc, 2026;15(1):e043736. PMID: 41432138.
- [pubmed] Zarei H, et al. "Diagnostic and Prognostic Value of Adrenomedullin in Acute Ischemic and Hemorrhagic Strokes: A Systematic Review and Meta-Analysis." Innov Clin Neurosci, 2026;23(1-3):47-53. PMID: 42027359.
- [pubmed] Cusack R, et al. "Mid-Regional Pro-Adrenomedullin as a Translational Biomarker of Microcirculatory Dysfunction in Sepsis: A Prospective Observational Study." Med Sci (Basel), 2026;14(1). PMID: 41892832.
- [pubmed] Ros-Córdoba F, et al. "Adrenomedullin is a good marker of severity and prognosis in patients with bronchiolitis." Eur J Pediatr, 2026;185(10). PMID: 42742823.
- [pubmed] Kitamura K, et al. "In Vitro and In Vivo Characterization of 40 kDa PEGylated Adrenomedullin in a DSS-Induced Colitis Model." Int J Mol Sci, 2025;26(19). PMID: 41096644.
Sources & Citations
Studies were read from their PubMed abstracts; DailyMed has no adrenomedullin label. Read October 7, 2026.
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