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phase 2Cardiovascular

Adrenomedullin

Also known as: ADM, AM, Adrenomedullin-52, pro-Adrenomedullin, MR-proADM

Adrenomedullin is a 52-amino acid endogenous vasodilatory peptide originally isolated from human pheochromocytoma tissue in 1993. It is one of the most potent endogenous vasodilators known and is produced by vascular endothelium, heart, lungs, kidneys, and adrenal medulla. Adrenomedullin exerts cardioprotective, vasodilatory, anti-inflammatory, and anti-microbial effects through the calcitonin receptor-like receptor (CLR) complexed with receptor activity-modifying proteins (RAMPs). Its mid-regional fragment (MR-proADM) has emerged as a powerful sepsis and heart failure prognostic biomarker.

4 cited references·6 researched benefits

Quick Answer

Adrenomedullin is a 52-amino acid peptide and one of the most potent endogenous vasodilators known. Produced by blood vessels, heart, and adrenal glands, it lowers blood pressure, protects the heart, reduces inflammation, and stabilizes vascular barriers. Its blood level (measured as MR-proADM) serves as a prognostic biomarker for sepsis and heart failure. Phase 2 trials are investigating adrenomedullin-targeted therapies for septic shock.

Key Facts

Mechanism
Adrenomedullin signals through the calcitonin receptor-like receptor (CLR) complexed with RAMP2 (forming the AM1 receptor) or RAMP3 (forming the AM2 receptor). Receptor activation stimulates adenylate cyclase, raising cAMP levels, and activates nitric oxide synthase to produce NO-mediated vasodilation. In endothelial cells, adrenomedullin strengthens endothelial barrier integrity by reorganizing tight junctions and adherens junctions through Rac1 GTPase activation. It reduces cardiomyocyte apoptosis via PI3K/Akt signaling, inhibits aldosterone secretion from the adrenal cortex, and suppresses inflammatory cytokine release from macrophages. Adrenomedullin also has direct bactericidal activity against gram-positive and gram-negative organisms through membrane disruption.
Research Status
phase 2
Half-Life
~22 minutes
Molecular Formula
C₂₅₇H₃₉₉N₇₃O₇₇S₅
Primary Use
Cardiovascular
Table of Contents

Benefits

  • Potent vasodilation — one of the strongest endogenous vasodilators, reducing systemic and pulmonary vascular resistancestrong
  • Cardioprotection — reduces cardiomyocyte apoptosis and cardiac fibrosis in ischemia-reperfusion injurymoderate
  • Endothelial barrier stabilization — prevents vascular leak in sepsis and acute lung injurymoderate
  • Anti-inflammatory — suppresses TNF-α, IL-6, and other inflammatory cytokinesmoderate
  • Prognostic biomarker — MR-proADM levels predict mortality in sepsis, pneumonia, and heart failurestrong
  • Direct antimicrobial activity against bacteria via membrane disruptionpreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous infusion (investigational)5-50 ng/kg/minContinuous infusionClinical studies in heart failure and sepsis have used escalating doses. Blood pressure monitoring required. Half-life of ~22 minutes supports continuous infusion.
Diagnostic (MR-proADM blood test)MR-proADM <0.75 nmol/L: low risk; 0.75-1.5 nmol/L: intermediate; >1.5 nmol/L: high riskAs clinically indicatedMid-regional pro-adrenomedullin (MR-proADM) is a stable surrogate for ADM levels. Used as a prognostic biomarker in sepsis, pneumonia, and heart failure. BRAHMS MR-proADM assay commercially available.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hypotension due to potent vasodilatory effectscommon
  • Tachycardia (reflex response to vasodilation)common
  • Flushing and facial warmthcommon
  • Headache from vasodilationcommon
  • Excessive diuresis and natriuresisrare
  • Severe hypotension requiring vasopressor supportserious

Frequently Asked Questions

What is adrenomedullin and where is it produced?
Adrenomedullin is a 52-amino acid peptide first isolated from pheochromocytoma (adrenal tumor) tissue in 1993. Despite its name, it is produced throughout the body — primarily by vascular endothelial cells, but also by cardiomyocytes, pulmonary epithelium, renal tubular cells, smooth muscle cells, and the adrenal medulla. Production increases dramatically during sepsis, heart failure, and other states of cardiovascular stress, where it functions as an endogenous protective mechanism. Its levels can rise 10-50 fold in septic shock.
How is MR-proADM used as a biomarker?
MR-proADM (mid-regional pro-adrenomedullin) is a stable fragment of the adrenomedullin precursor molecule. Because adrenomedullin itself has a short half-life and binds to plasma proteins, MR-proADM is measured instead as a reliable surrogate. It is used clinically as a prognostic biomarker in community-acquired pneumonia (PRORATA and TRIAGE studies), sepsis (predicts organ failure and mortality), and heart failure (independent predictor of adverse outcomes). The BRAHMS MR-proADM Kryptor assay is commercially available and increasingly integrated into emergency department protocols.
Is adrenomedullin being developed as a treatment for sepsis?
Yes. Adrenomedullin-targeted therapy is under active clinical investigation for septic shock. The key therapeutic approach is Adrecizumab (HAM8101), a non-neutralizing anti-adrenomedullin antibody that binds the N-terminal region of circulating ADM. Rather than blocking ADM activity, Adrecizumab acts as a carrier that redistributes ADM from the bloodstream to the vascular endothelium where it stabilizes endothelial barriers and prevents capillary leak. The AdrenOSS-2 phase 2 trial in septic shock patients with elevated ADM showed promising reductions in organ failure. Phase 3 trials are planned.
How does adrenomedullin relate to CGRP?
Adrenomedullin belongs to the calcitonin gene-related peptide (CGRP) superfamily, which also includes calcitonin, amylin, and intermedin/adrenomedullin-2. All family members share structural features including a six-residue ring formed by a disulfide bond and an amidated C-terminus. They signal through related receptors: CGRP uses CLR/RAMP1, while adrenomedullin uses CLR/RAMP2 and CLR/RAMP3. Both are potent vasodilators, but adrenomedullin has stronger endothelial barrier-protective effects, while CGRP is more involved in pain signaling and migraine pathophysiology.

References

  1. 1
    Isolation and identification of adrenomedullin from a pheochromocytoma(1993)PubMed ↗
  2. 2
    Adrenomedullin in cardiovascular disease: from bench to bedside(2005)PubMed ↗
  3. 3
    Mid-regional pro-adrenomedullin as a prognostic biomarker in sepsis: systematic review(2014)PubMed ↗
  4. 4
    Adrecizumab (anti-adrenomedullin antibody) in sepsis: AdrenOSS-2 trial results(2020)PubMed ↗

Latest Research

Last updated: 2026-02-19