Adrenomedullin

ADM, AM, proADM (precursor); bio-ADM (biologically active ADM assay); MR-proADM (mid-regional pro-adrenomedullin)

Cardiovascular & circulation

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Summary

Class: Naturally occurring 52-amino-acid peptide hormone of the calcitonin/CGRP family, cleaved from preproadrenomedullin along with PAMP
Mechanism: Binds calcitonin-receptor-like receptor paired with RAMP2 or RAMP3, raises cAMP, widens blood vessels and — importantly — stabilises the barrier between blood and tissue
Routes studied: Intravenous infusion (human physiology and small clinical studies); inhaled (pulmonary hypertension studies, Japan); rectal/IV recombinant peptide in small inflammatory bowel studies. No self-administered route
Half-life: Very short — roughly 20 minutes in plasma, which is why development has focused on antibodies against it rather than giving the peptide
Storage: Research peptide; lyophilised material refrigerated or frozen. Not a consumer product
Regulatory status: Not approved anywhere as a medicine. Related diagnostic assays (MR-proADM, bio-ADM) are in clinical use in parts of Europe †

Doses are as reported in studies or by the community — never recommendations.

1What it is

Adrenomedullin is a hormone your own body makes. It was found in 1993 in tissue from an adrenal tumour (a pheochromocytoma), which is where the name comes from, but the main sources in healthy people are the cells lining blood vessels and the heart. Levels rise sharply in sepsis, heart failure and other states where the circulation is under strain, and how high they rise predicts how badly patients do.

That dual character is what makes it unusual. Adrenomedullin inside the blood vessel appears protective — it keeps the vessel wall sealed. Adrenomedullin outside the vessel, in the tissue, drops blood pressure. So the therapeutic question has not been "how do we give more of it" but "how do we keep it in the right compartment". This is a research and hospital-medicine molecule, not a peptide with a self-directed user base. Community use: essentially none documented.

2How it's thought to work

Signals through CLR (calcitonin receptor-like receptor) in combination with accessory proteins RAMP2 (the AM1 receptor) or RAMP3 (AM2), raising cyclic AMP inside the cell.

Tightens the endothelial barrier by stabilising the actin cytoskeleton and cell-to-cell junctions, reducing the capillary leak that drives shock.

Dilates arteries, partly through nitric oxide, lowering blood pressure and afterload.

Has natriuretic and diuretic effects on the kidney and suppresses aldosterone.

Knockout animals die in utero from vascular and lymphatic defects, which tells you how fundamental the pathway is to vessel development.

Adrenomedullin at a receptor built from the calcitonin receptor-like receptor with its RAMP2 accessory protein — the accessory subunit is what gives the receptor this ligand. The vessel widens, and the endothelial barrier is held shut rather than opened.Schematic — not to scale

3What the research shows

Biomarker value in sepsis and heart failure

The best-established human finding is not a treatment effect at all. Circulating bio-ADM and MR-proADM track severity and predict mortality and need for vasopressors in sepsis, and predict outcomes in acute heart failure, across multiple large observational cohorts (Marino 2014, Crit Care; Maisel 2010–2012 BACH substudies, J Am Coll Cardiol and related). [3]

Graded A (neutral)

Adrecizumab (enibarcimab) in septic shock

Adrecizumab is a monoclonal antibody that binds the N-terminus of adrenomedullin without fully blocking it; the idea is that it holds the peptide in the bloodstream where it is protective. The Phase 2 AdrenOSS-2 trial in patients with septic shock and high bio-ADM was safe and reported favourable signals on organ-support measures, but was not a definitive efficacy trial (Laterre 2021, Intensive Care Med). A larger confirmatory programme followed; readouts and current status should be checked against the sponsor and registry entries †. [4]

Short human infusions

Infusing adrenomedullin into healthy volunteers and into patients with heart failure or hypertension lowers systemic vascular resistance, raises cardiac output and increases urine sodium, with dose-limiting hypotension and flushing (Nagaya 2000, Circulation; Troughton 2000 and related small studies). These are physiology experiments lasting hours. [2]

Inhaled adrenomedullin in pulmonary hypertension

Small Japanese studies reported selective reduction in pulmonary vascular resistance after inhalation (Nagaya 2003–2004). Not developed further into a licensed product.

Graded B (very small)

Inflammatory bowel disease

Pilot studies of recombinant human adrenomedullin infusion in refractory ulcerative colitis and Crohn's disease, mostly from one Japanese group, reported symptomatic and endoscopic improvement in small numbers of patients. Early-stage and not independently replicated at scale.

Graded C/D

Cardioprotection, lymphangiogenesis, pre-eclampsia

Extensive animal and cell work. Reduced adrenomedullin signalling is implicated in pre-eclampsia and in lymphatic disorders; none of this has produced a human treatment.

4Reported side effects and interactions

Literature-reported

In human infusions the predictable effects are hypotension, reflex tachycardia, flushing and headache — the expected consequences of a potent vasodilator. Adrecizumab was reported well tolerated in Phase 1 and 2.

Community-reported

None. The compound is not in self-directed use.

Theoretical. Giving a strong vasodilator to someone already hypotensive is the central hazard, and is exactly why the antibody strategy was chosen over the peptide. Adrenomedullin is also expressed by many tumours and supports , so sustained exogenous exposure carries the same unstudied oncological caution as other pro-angiogenic peptides.

Interactions. Additive hypotension with any vasodilator, nitrate, ACE inhibitor, ARB or diuretic. No formal interaction studies exist.

Markers researchers commonly monitor

In the clinical research setting these are protocol-mandated rather than optional:

Marker	Why it's watched
Blood pressure, continuously or near-continuously	the dose-limiting effect is hypotension; this is the primary safety measure.
Heart rate	reflex tachycardia accompanies the vasodilation.
bio-ADM or MR-proADM	the pathway's own biomarker; used to select patients and to track target engagement.
Lactate and vasopressor requirement	in sepsis studies these are the outcomes the mechanism is meant to improve.
Creatinine, eGFR and urine output	the peptide is natriuretic and the kidney is a target organ.
Fluid balance and markers of capillary leak (albumin, haematocrit)	the barrier-stabilising mechanism predicts changes here.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable in the usual sense: adrenomedullin is handled as a hospital or laboratory research infusion prepared by pharmacy or investigators, with dosing in ng/kg/min against continuous blood-pressure monitoring. There is no established vial format, no community practice, and nothing here that the calculator is built for.

6Commonly studied alongside

CGRP (#159 — same receptor family and accessory proteins), natriuretic peptides such as BNP and ANP (as co-biomarkers in heart failure), urocortin 2 (#155 — the other vasoactive peptide trialled in acute heart failure), apelin (#152).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Investigational only
European Union	Not authorised as a medicine; MR-proADM and bio-ADM diagnostic assays are CE-marked and used in some hospitals †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA. A vasodilatory peptide hormone with no performance rationale; check the current list

8Open questions

Does stabilising adrenomedullin in the circulation change hard outcomes in septic shock, or only surrogate measures?
Can the vascular-sealing effect be separated from the blood-pressure-lowering effect pharmacologically?
What is the long-term safety of chronic pathway modulation given adrenomedullin's role in tumour ?
Is bio-ADM useful as a treatment-selection biomarker outside intensive care?

9References

1Kitamura K et al. (1993). Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. PubMed · DOI
2Nagaya N et al. (2000). Haemodynamic and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation. PubMed · DOI
3Marino R et al. (2014). Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis. Crit Care. PubMed · DOI
4Laterre PF et al. (2021). 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. PubMed · DOI
5Geven C, Bergmann A, Kox M, Pickkers P (2018). Vascular effects of adrenomedullin and the anti-adrenomedullin antibody adrecizumab in sepsis. Shock. PubMed · DOI
6Ashizuka S et al. (2013–2021). Adrenomedullin therapy in patients with refractory ulcerative colitis — pilot studies. J Gastroenterol / Inflamm Bowel Dis [verify which]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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