Adrenomedullin
Also known as: ADM, AM, adrenomedullin-1, adrenomedullin 1-52, CGRP family peptide
Endogenous vasoactive peptide hormone — 52-amino-acid member of the calcitonin gene-related peptide (CGRP) superfamily; potent vasodilator, endothelial barrier
What it is
People with heart failure, sepsis, or pulmonary hypertension often have critically disrupted blood flow and vascular tone — adrenomedullin is a naturally occurring peptide that researchers are studying for its ability to powerfully dilate blood vessels, protect the endothelial lining, and support kidney function during acute cardiovascular crises.
The scientific side
adrenomedullin (AM) is a 52-amino-acid peptide hormone originally isolated from human adrenal medullary pheochromocytoma tissue and subsequently found to be expressed widely in vascular endothelial cells, vascular smooth muscle, cardiac tissue, kidney, lung, and adrenal glands. AM belongs to the calcitonin gene-related peptide (CGRP) superfamily and exerts its actions primarily through binding to the calcitonin receptor-like receptor (CALCRL) in complex with receptor activity-modifying proteins 2 and 3 (RAMP2/RAMP3), activating adenylyl cyclase and raising intracellular cyclic AMP (cAMP) in target cells. In vascular smooth muscle, elevated cAMP activates protein kinase A (PKA), reducing intracellular calcium and producing dose-dependent vasodilation — the peptide's most clinically prominent action. Studies reviewed here consistently report that intravenous AM infusion at doses of 2.9–15 ng/kg/min in humans produces reductions in mean arterial pressure, systemic and pulmonary vascular resistance, and increases in cardiac output, with effects measurable within minutes of infusion onset. AM also has potent endothelial barrier-stabilizing actions: by activating cAMP/PKA pathways in endothelial cells, it reinforces tight junctions and adherens junction proteins, reduces vascular permeability, and protects against inflammatory edema — a mechanism particularly relevant in sepsis and ARDS, where endothelial barrier disruption drives organ failure. In the kidney, AM promotes natriuresis and diuresis partly through direct tubular actions and partly through inhibition of the renin-angiotensin-aldosterone system: AM suppresses renin secretion, inhibits aldosterone synthesis, and counteracts antidiuretic hormone-mediated water reabsorption. Plasma AM levels are markedly elevated in critical illness states including sepsis, heart failure, pulmonary hypertension, myocardial infarction, and ARDS, reflecting both endogenous compensatory production and pathological vascular dysfunction. Bioactive adrenomedullin (bio-ADM) circulates at much lower concentrations than total immunoreactive AM because the mature peptide is rapidly cleared — its plasma half-life is approximately 22 minutes in humans — and is found largely bound to complement factor H. The stable precursor fragment mid-regional pro-adrenomedullin (MR-proADM) is used clinically as a surrogate biomarker. In animal models of heart failure and experimental endotoxemia, exogenous AM infusion improves cardiac output, reduces pulmonary vascular resistance, augments renal sodium excretion, and attenuates inflammatory responses, consistent with its endogenous compensatory role during acute hemodynamic stress.
Class: Endogenous vasoactive peptide hormone — 52-amino-acid member of the calcitonin gene-related peptide (CGRP) superfamily; potent vasodilator, endothelial barrier stabilizer, and cardiovascular regulator
Administration & storage
- Administration
- Intravenous continuous infusion — the only validated route in published human studiesrequired due to AM's approximately 22-minute plasma half-lifeControlled-rate infusion pump at hospital or ICU bedside in all clinical trial settingsIntrapulmonary infusion in catheterization laboratory settings for pulmonary vascular response studies (specialized research only)Inhaled delivery of pegylated adrenomedullin (PEG-ADM) investigated in Phase 2 ARDS trial (NCT04417036) — this is a modified derivativenot native AM
- Storage
- Research-grade synthetic adrenomedullin peptide is typically stored as lyophilized powder at −20°C or −80°C in aliquots under desiccating conditions to prevent moisture-induced degradation. Reconstituted solutions should be prepared freshly immediately before infusion and used within 24 hours if stored at 2–8°C; stability data for extended storage in solution have not been comprehensively validated in the publicly available literature for research-grade preparations. Avoid repeated freeze-thaw cycles. No commercial product stability data are available for North American markets as no approved product exists.
- Cautions
- Dose-dependent hypotension: IV AM produces significant blood pressure reduction at research doses; high-dose infusion (5.8 pmol/kg/min) reduced systolic BP by up to 24.6 mmHg and diastolic BP by 21.9 mmHg in hypertensive patients (PMID 11040240). Close hemodynamic monitoring required.,Reflex tachycardia: Heart rate increases of 10–18 bpm have been documented consistently across dosing studies in healthy volunteers and hypertensive patients (PMIDs 11040240, 10720032, 9176019). Caution in patients with tachyarrhythmias or limited cardiac reserve.,Sympathoadrenal activation: Plasma norepinephrine increased approximately 50% at high research doses without a commensurate aldosterone response, indicating dissociated RAAS/sympathetic activation (PMID 10720032). Clinical implications in patients on vasopressors or sympathomimetics are unknown.,ECG abnormalities: Slight ECG abnormalities were observed in the single-dose Phase 1 trial at doses up to 15 ng/kg/min (PMID 32021087). Cardiac rhythm monitoring is required during any IV administration.,Interaction with angiotensin II vasopressor response: In a controlled crossover study, background AM infusion at 4 pmol/min/kg significantly attenuated the blood pressure response to exogenous angiotensin II (PMID 11410122). This is relevant in critical care settings where AM elevations may blunt vasopressor efficacy.,No safety data in women, children, elderly, or patients with severe hepatic or renal impairment beyond very limited pilot studies. Phase 1 data are restricted to healthy adult males (PMID 32021087).,Compounded or grey-market adrenomedullin is not validated for human use — peptide purity, sterility, and dosing accuracy cannot be guaranteed outside approved research settings.
Legal & regulatory status
Adrenomedullin is not approved by the US FDA as a therapeutic agent. Native adrenomedullin has no FDA-approved indication, drug approval number, or authorized commercial formulation in the United States. A Phase 1…
Adrenomedullin is not currently listed as a prohibited substance on the WADA Prohibited List (2024). As an endogenous vasoactive peptide, native adrenomedullin does not appear under Section S2 (Peptide Hormones, Growth…
Adrenomedullin is not approved by Health Canada as a therapeutic agent and carries no Drug Identification Number (DIN) for commercial use in Canada. No Canadian clinical trial registry entries exist for therapeutic…
What it's studied for
- Cardiovascular risk stratification in acute coronary syndromes — bio-ADM as a prognostic biomarker Prospective Cohort (multicenter, n=4,922 patients)
- Sepsis diagnosis and organ failure prediction — MR-proADM as a critical illness biomarker Retrospective Cohort / Established Clinical Biomarker
- Acute decompensated heart failure — intravenous AM infusion for hemodynamic support Pilot Clinical Study / Phase 1–2
- Pulmonary arterial hypertension — AM infusion for pulmonary vascular resistance reduction Small Clinical Studies / Phase 1–2
- Cardiac amyloidosis prognosis — bio-ADM as an independent mortality predictor Multicenter Observational Cohort (n=210 patients, cross-continental)
- COVID-19 critical illness — bio-ADM for mortality and dialysis requirement prediction Prospective Cohort Pilot (n=119 ICU patients)
- Essential hypertension — AM infusion hemodynamic and hormonal effects Placebo-Controlled Crossover Clinical Trial
- Acute respiratory distress syndrome (ARDS) — inhaled PEG-ADM (investigational, futility established) Phase 2 Randomized Controlled Trial (n=90 patients)
Safety signals
- Clinically significant hypotension
- Reflex tachycardia and increased heart rate
- ECG abnormalities
- Elevated plasma renin activity without aldosterone response — dissociated RAAS activation
- Sympathoadrenal activation — elevated plasma norepinephrine
- Headache leading to study withdrawal
- Attenuation of angiotensin II vasopressor response
- Prolactin elevation following IV infusion
- Absence of natriuretic effect at typical research doses — potential for misleading diuretic expectations
All studies (7)
Frequently asked
Has adrenomedullin been approved as a drug anywhere in the world?
As of the research date for this entry, native adrenomedullin (AM) has not been approved as a therapeutic drug in the United States, Canada, the European Union, or any other major regulatory jurisdiction. It remains an investigational compound. A related peptide, carperitide (recombinant human atrial natriuretic peptide), is approved in Japan for acute heart failure, but carperitide is a different molecule. Anti-adrenomedullin antibody therapies such as enibarcimab are currently in Phase 2 clinical development. Anyone presenting adrenomedullin for purchase or use as a therapeutic outside a licensed clinical trial is operating outside approved regulatory frameworks.
What does adrenomedullin actually do in the body?
Adrenomedullin is an endogenous peptide that your body naturally produces in blood vessel walls, the heart, lungs, and kidneys. Its primary actions include relaxing blood vessels (vasodilation), stabilizing the inner lining of blood vessels (endothelial barrier protection), promoting sodium and water excretion by the kidneys (natriuresis), and modulating stress hormone systems including the renin-angiotensin-aldosterone system. In critical illness such as sepsis or severe heart failure, the body sharply increases AM production as a compensatory response — which is why elevated levels serve as a prognostic biomarker in ICU settings. The peptide acts through receptors on vascular smooth muscle and endothelial cells, raising intracellular cyclic AMP levels to produce its relaxing effects.
Can adrenomedullin be used for performance enhancement or bodybuilding?
There is no published clinical evidence supporting adrenomedullin use for athletic performance enhancement, muscle growth, or bodybuilding. AM's principal actions are cardiovascular — vasodilation, blood pressure reduction, and endothelial protection — not anabolic. Its extremely short plasma half-life (approximately 22 minutes in humans) means effects cease rapidly after infusion stops, and it can only be administered intravenously in clinical settings. WADA does not currently list adrenomedullin as a prohibited substance because no performance-enhancing mechanism has been established. Any non-medical use of this investigational peptide would carry uncharacterized risks and no validated benefit.
What blood pressure effects should be expected from adrenomedullin infusion?
Published clinical studies consistently show that intravenous adrenomedullin causes dose-dependent reductions in blood pressure. In hypertensive patients at research doses (5.8 pmol/kg/min), systolic blood pressure fell approximately 24.6 mmHg and diastolic pressure fell approximately 21.9 mmHg. In healthy volunteers at 2–8 ng/min/kg, mean arterial pressure fell approximately 7.7 mmHg. These hypotensive effects are accompanied by compensatory reflex increases in heart rate of 10–18 beats per minute. The hypotension occurred without the usual compensatory sympathetic nervous system activation seen with other vasodilators, which makes adrenomedullin's cardiovascular profile unusual. These are effects documented in strictly controlled clinical research settings with continuous monitoring.
Is MR-proADM the same thing as adrenomedullin, and can I get it tested?
MR-proADM (mid-regional pro-adrenomedullin) is not the active peptide itself — it is a stable precursor fragment produced when the body makes adrenomedullin. Because the mature bioactive AM is rapidly cleared from blood (half-life ~22 minutes), MR-proADM is much easier to measure reliably in plasma and serves as a surrogate marker for AM production. Clinically, MR-proADM is used in some hospital laboratory settings as a prognostic biomarker in sepsis, heart failure, and critical illness — it is not a direct marker of any specific disease but rather reflects overall systemic stress and vascular dysfunction. Commercial MR-proADM testing is available through some specialty reference laboratories. If you are interested in this test, a physician who manages critical illness or heart failure would be the appropriate referral.
Why was the Bayer inhaled adrenomedullin (PEG-ADM) trial stopped?
The SEAL trial (NCT04417036) evaluated inhaled pegylated adrenomedullin (PEG-ADM, BAY 1097761) in patients with acute respiratory distress syndrome (ARDS). In Part A of the trial, the drug was found to be well tolerated — the stopping decision was not due to safety concerns. However, the drug failed to show clinical benefit on the primary endpoint (clinical utility index), and ventilator-free survival at Day 28 was actually numerically lower in the 960 µg group (52%) than in placebo (65%). Based on these results, Bayer decided not to continue into Part B of the trial. This is an important example of a biologically plausible therapy that did not translate to patient benefit in this specific indication, disease stage, and delivery approach. Research into adrenomedullin's role in lung and vascular protection continues through other mechanisms and formulations.