Adrenomedullin
Also known as: ADM, Adrecizumab target peptide, Adrenomedullin-2, Adrenomedullin‑1, AM, hAM(1-52), Peptide hormone adrenomedullin, Proadrenomedullin-derived peptide
Source Adrenomedullin at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
Adrenomedullin (ADM) is a vasoactive peptide of the calcitonin/CGRP family that circulates in a biologically inactive pro‑form (mid‑regional pro‑ADM). It is being investigated for its role as a biomarker of infection severity, heart‑failure congestion, and endothelial barrier integrity, and as a potential therapeutic target in cardiovascular and metabolic disease.
Mechanism of Action
ADM binds to the calcitonin‑receptor‑like receptor complexed with receptor‑activity‑modifying proteins (RAMP2/3), activating adenylate cyclase and raising intracellular cAMP. This signaling induces potent vasodilation, reduces vascular tone, and stabilises endothelial junctions by influencing VE‑cadherin and the angiopoietin‑Tie2 axis, thereby limiting capillary leak during systemic inflammation.
What the Research Shows
A 2024 review of hospital‑acquired pneumonia highlighted mid‑regional pro‑ADM as an inflammatory biomarker that improves risk stratification. A 2022 heart‑failure biomarker consensus described bio‑ADM and MR‑pro‑ADM as useful for assessing systemic and pulmonary congestion. A 2022 cellular review identified ADM as a key regulator of endothelial permeability in systemic inflammation. Proteomic and Mendelian‑randomisation analysis (2022) found higher circulating ADM to be causally protective against incident heart failure, supporting its druggability. A 2014 diabetes review reported elevated ADM levels in both type‑1 and type‑2 diabetes, correlating with renal, retinal, and vascular complications, and suggested that reducing ADM might mitigate these outcomes.
Reported Benefits
Current evidence suggests ADM measurements can aid early identification of severe infection and fluid overload in heart failure, potentially guiding therapy. Genetic and proteomic data indicate a protective causal role for higher ADM levels in heart‑failure development, making it an attractive target for drug development. In diabetes, ADM may serve as a marker of disease burden and complication risk.
Limitations of the Evidence
Most data are observational or derived from reviews; randomized interventional studies of ADM modulation are lacking. Biomarker utility varies across settings and cut‑off values are not standardised. The protective effect in heart failure is inferred from Mendelian‑randomisation, which does not replace clinical trial evidence. Therapeutic strategies to lower ADM in diabetes remain speculative.
Safety Considerations
Endogenous ADM mediates vasodilation; exogenous administration could cause hypotension, reflex tachycardia, and flushing. No adverse‑event data are provided in the cited literature for investigational ADM‑targeting agents. Caution is warranted in patients with baseline low blood pressure or those receiving other vasodilators. Monitoring of hemodynamic parameters would be prudent in any clinical trial setting.
How It Is Administered
ADM‑based therapeutics are investigational and have been studied via intravenous or subcutaneous routes. Formulations are typically peptide solutions suitable for parenteral delivery. Detailed dosing regimens have not been established in the cited literature.
Routes of Administration
Goals & Uses
- Heart failureCardiovascularLow
- Preeclampsia preventionObstetricsLow
- Renal protectionRenalLow
- Sepsis therapyCritical CareModerate
- Vasodilation / Hypotensive effectCardiovascularHigh
- Inflammatory bowel diseaseGastroenterologyModerate
- Pulmonary hypertensionCardiovascularModerate
- Septic shock treatmentCritical CareModerate
- AngiogenesisTissue RepairModerate
- Cardioprotection / Heart failureCardiovascularModerate
- VasodilationCardiovascular SupportModerate
Contraindications
- Severe hypotension / HypovolemiaCardiovascularHigh
- Known hypersensitivity to adrenomedullinImmunologicalHigh
- Hypertrophic obstructive cardiomyopathyCardiovascularModerate
- Severe aortic stenosisCardiovascularHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- Injection site reactionsLocalUncommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- Flushing / Facial flushingDermatologicalCommon
- HypotensionCardiovascularCommonLow blood pressure
- FlushingVascularUncommonWarmth and redness of the skin
- TachycardiaCardiovascularCommonAbnormally fast heart rate
- NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
- Tachycardia / Reflex tachycardiaCardiovascularCommon
Drug Interactions
- NitratesModerate
- Phosphodiesterase inhibitors (e.g., sildenafil)Moderate
- Antihypertensive agentsModerate
- Beta‑blockersLow
- Other vasodilators (e.g., nitroglycerin)Moderate
- Vasopressors (e.g., norepinephrine)Moderate
- DiureticsLowMay worsen dehydration or electrolyte imbalance
Population Constraints
- PregnancyReproductive SafetyRelative
- Hepatic impairmentOrgan FunctionRelative
- Renal impairmentOrgan ImpairmentRelative
- Severe renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionUnapprovedNo marketing authorization.
- United StatesUnapprovedInvestigational use only in clinical trials.
- United KingdomInvestigationalNo MHRA approval. Participates in multinational investigational trials.
Not approved as a therapeutic agent in any jurisdiction; studied in preclinical and early‑phase clinical trials.
Evidence & Sources
- Journal ArticleModerateMiron M, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateNúñez J, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateHellenthal KEM, Brabenec L, Wagner NM2022-01-01T00:00:00.000000Z
- Journal ArticleHighHenry A, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateWong HK, et al.2014-01-01T00:00:00.000000Z
Frequently Asked Questions
Is adrenomedullin an approved drug for any condition?
No. All references describe ADM as an investigational peptide or a circulating biomarker. It has not received regulatory approval for therapeutic use.
How is adrenomedullin measured in clinical practice?
The peptide is usually quantified as its stable fragment, mid‑regional pro‑adrenomedullin, using immunoassays on plasma samples. This approach is employed in studies of infection and heart failure.
Could lowering adrenomedullin improve diabetes outcomes?
A 2014 review notes that high ADM levels correlate with diabetic complications, but it only proposes that reducing ADM might be beneficial. No clinical trials testing this hypothesis have been reported.
What makes adrenomedullin a promising heart‑failure target?
Proteomic and Mendelian‑randomisation analyses identified higher circulating ADM as causally protective against incident heart failure, and ongoing trials are evaluating ADM‑focused therapies, indicating translational interest.
Are there risks associated with using adrenomedullin as a therapy?
Because ADM is a potent vasodilator, therapeutic use could lead to low blood pressure, dizziness, or reflex tachycardia. Safety data are limited, so careful monitoring would be required in any experimental setting.
What is Adrenomedullin?
Adrenomedullin (ADM) is a vasoactive peptide of the calcitonin/CGRP family that circulates in a biologically inactive pro‑form (mid‑regional pro‑ADM). It is being investigated for its role as a biomarker of infection severity, heart‑failure congestion, and endothelial barrier integrity, and as a potential therapeutic target in cardiovascular and metabolic disease.
What is Adrenomedullin used for?
Adrenomedullin is educationally associated with: Heart failure, Preeclampsia prevention, Renal protection, Sepsis therapy, Vasodilation / Hypotensive effect, Inflammatory bowel disease, Pulmonary hypertension, Septic shock treatment, Angiogenesis, Cardioprotection / Heart failure, Vasodilation. Educational only — not medical advice.
How is Adrenomedullin administered?
Recorded routes of administration: Intraperitoneal, Intravenous, Subcutaneous.
What are the potential side effects of Adrenomedullin?
Reported adverse effects include: Injection site reactions, Headache, Flushing / Facial flushing, Hypotension, Flushing, Tachycardia, Nausea, Tachycardia / Reflex tachycardia. This list is not exhaustive — consult a qualified clinician.
Who should avoid Adrenomedullin?
Recorded contraindications: Severe hypotension / Hypovolemia, Known hypersensitivity to adrenomedullin, Hypertrophic obstructive cardiomyopathy, Severe aortic stenosis, Severe hypotension. Consult a qualified clinician before use.