Adrenomedullin

Summary

Adrenomedullin (AM) is an endogenous 52-amino acid peptide originally isolated from human pheochromocytoma tissue. It is a multifunctional vasoactive peptide with potent vasodilatory, cardioprotective, anti-inflammatory, and angiogenic properties. Endogenous AM plays roles in cardiovascular homeostasis, fluid balance, and immune modulation. Synthetic/recombinant forms are under clinical investigation for conditions such as septic shock, pulmonary hypertension, inflammatory bowel disease, and preeclampsia.

Mechanism of Action

Binds to calcitonin receptor-like receptor (CLR) complexed with receptor activity-modifying proteins (RAMP2 or RAMP3), activating adenylyl cyclase via Gs proteins, increasing intracellular cAMP. Produces potent vasodilation, natriuresis, inhibition of aldosterone secretion, anti-inflammatory and anti-apoptotic effects, and promotes angiogenesis and lymphangiogenesis.

Routes of Administration

Goals & Uses

• Preeclampsia preventionObstetricsLow
• Vasodilation / Hypotensive effectCardiovascularHigh
• Inflammatory bowel diseaseGastroenterologyModerate
• Pulmonary hypertensionCardiovascularModerate
• Septic shock treatmentCritical CareModerate
• Cardioprotection / Heart failureCardiovascularModerate

Contraindications

• Severe hypotension / HypovolemiaCardiovascularHigh
• Known hypersensitivity to adrenomedullinImmunologicalHigh
• Hypertrophic obstructive cardiomyopathyCardiovascularModerate
• Severe aortic stenosisCardiovascularHigh

Adverse Effects

• Injection site reactionsLocalUncommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• Flushing / Facial flushingDermatologicalCommon
• HypotensionCardiovascularCommonLow blood pressure
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Tachycardia / Reflex tachycardiaCardiovascularCommon

Drug Interactions

• Phosphodiesterase inhibitors (e.g., sildenafil)Moderate
• Antihypertensive agentsModerate
• Vasopressors (e.g., norepinephrine)Moderate
• DiureticsLowMay worsen dehydration or electrolyte imbalance

Population Constraints

• PregnancyReproductive SafetyRelative
• Hepatic impairmentOrgan FunctionRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionInvestigationalStudied under European CTA frameworks; adrecizumab (anti-AM antibody) completed Phase II (AdrenOSS-2) for septic shock. Orphan designation not yet granted for AM itself.
• United StatesInvestigationalNo FDA-approved indication. Investigated under IND for sepsis, pulmonary hypertension, and IBD.
• United KingdomInvestigationalNo MHRA approval. Participates in multinational investigational trials.

Not approved by FDA, EMA, or MHRA for any indication. Investigated under various IND/CTA frameworks. Humanin AM analogues and bispecific antibody approaches (e.g., adrecizumab targeting the AM pathway) have entered Phase II trials in septic shock.

Evidence & Sources

No sources recorded yet.