Adrenomedullin 2
The third member of the adrenomedullin and CGRP receptor family: where it is found, what it does in animals, and what its blood level marks
Adrenomedullin 2, also called intermedin, was found in 2004 as a new member of the CGRP peptide family. It acts on the same receptors as adrenomedullin and CGRP, widens blood vessels and protects heart, kidney and gut tissue in animal studies, yet raises blood pressure when it acts inside the brain. In people it has only been measured: its blood level rises in heart failure and acute coronary syndromes and carries prognostic information there. It has never been tested as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Adrenomedullin 2 has not been given to people in any study we found. The human evidence is measurement only: blood levels in healthy adults and in heart failure, coronary syndromes, diabetes, dialysis and cancer, staining of autopsy tissue, a gene-variant cohort, and experiments on donated human cells and arteries.
What is it?
Adrenomedullin 2 belongs to the calcitonin family alongside CGRP, adrenomedullin and amylin. Two groups found it independently in 2004, which is why it carries two names: adrenomedullin 2 and intermedin. It is cut from a larger precursor into several active pieces, the longest 53 amino acids. This page covers adrenomedullin 2 itself; adrenomedullin, the older and better-studied relative, has its own entry.
Its receptors are the same ones CGRP and adrenomedullin use: a protein called CLR paired with one of three helper proteins (RAMP1, RAMP2 or RAMP3). Early work described adrenomedullin 2 as unselective among them. A 2023 study found a subtler preference: it binds the CLR-RAMP3 pair about as tightly as adrenomedullin does but stays bound much longer, so its signal there lasts longer.
In animals its effects depend on where it acts. In the circulation it widens vessels and lowers blood pressure; injected into the brain it raises pressure and heart rate through the sympathetic nerves and reduces eating and drinking. In rodent models it protected the heart from ischaemia, eased sepsis, improved insulin resistance in obese mice and calmed gut inflammation through immune cells in the bowel wall. It is not uniformly protective: in breast cancer models it helped tumours grow and spread, and blocking it slowed them.
In people the evidence is measurement. Plasma levels are low in healthy adults and higher in heart failure, especially with kidney impairment. High levels on admission predicted cardiac events after ST-elevation and non-ST-elevation heart attacks, and higher preoperative levels predicted worse outcomes in breast cancer. A variant in the gene was linked to higher blood pressure, weaker kidney function and silent brain infarcts in a Japanese cohort.
One caution runs through these studies: different assays give very different numbers. Healthy plasma read about 6 pg/mL in one radioimmunoassay study and over 100 pg/mL in others, so figures from one paper cannot be compared with another's. None of the human studies gave adrenomedullin 2 to anyone, and there is no product, trial or approved use.
Mechanism of Action
Adrenomedullin 2 works through the same receptor family as CGRP and adrenomedullin, raising cAMP in target cells; which effect wins depends on the tissue and on where in the body it acts.
CLR-RAMP receptors
It activates CLR paired with RAMP1, RAMP2 or RAMP3, and holds on longest to the CLR-RAMP3 (AM2) receptor, prolonging its signal there.
Vessel widening
In the circulation of rats and mice it relaxes blood vessels and lowers pressure; in human tissue it relaxed uterine arteries in pregnancy.
Central effects
Acting inside the rat brain it raises blood pressure and heart rate through sympathetic nerves and reduces food and water intake.
Tissue protection in models
In cells and rodents it protected heart cells from ischaemia, tightened leaky vessel walls in sepsis and promoted protective immune cells in the gut.
Published Research
These are studies of adrenomedullin 2 (intermedin) read from their PubMed abstracts: human measurement studies in heart disease, diabetes, dialysis, cancer and children with postural tachycardia, a gene-variant cohort, work on human tissue and cells, the animal studies that established its actions, and three reviews. No study gave it to people.
Low in healthy blood, higher in heart failure
In 75 healthy people, plasma adrenomedullin 2 averaged 6.3 pg/mL, about a quarter of the adrenomedullin level, and the two moved together; fragments of its precursor circulated at higher levels than the active peptide. In 19 patients with systolic heart failure it averaged 9.8 pg/mL, reached 11.3 pg/mL in those whose kidneys were also impaired, and tended to fall after six months of cardiac resynchronization therapy.
Found in the human hypothalamus, heart and kidney
Autopsy tissue stained for adrenomedullin 2 in nerve cells of the paraventricular and supraoptic nuclei of the hypothalamus, where it sat alongside vasopressin, and in heart muscle cells and kidney tubule cells, but not in glomeruli or blood vessel walls. Its messenger RNA was detected in brain, pituitary, heart and kidney.
A gene variant tied to blood pressure and kidney function
In 1,073 Japanese adults from the Ohasama cohort, people carrying two copies of the deletion form of an insertion/deletion variant in the adrenomedullin 2 gene had higher 24-hour systolic pressure (127.4 versus about 122 mm Hg) and lower kidney filtration than the other genotypes. Compared with two copies of the insertion form, they had 2.7 times the odds of chronic kidney disease and 2.4 times the odds of silent lacunar brain infarcts.
A risk marker after ST-elevation heart attack
Plasma adrenomedullin 2 was higher in 128 patients with ST-elevation myocardial infarction than in 128 healthy controls. Over six months, a high level independently predicted major adverse cardiovascular events; on its own it predicted about as well as the GRACE risk score, and adding it to that score improved the prediction.
A risk marker in non-ST-elevation coronary syndromes
In 132 patients admitted with non-ST-elevation acute coronary syndrome, the median level (320 pg/mL) was above that of 132 matched controls (227 pg/mL). Twenty-three patients had a major cardiac event over a mean of 227 days; a level above the study's 340.7 pg/mL cutoff carried about 13 times the risk after adjustment for NT-proBNP and other risk factors, and its predictive accuracy was similar to NT-proBNP's.
Raised in type 2 diabetes but a poor diagnostic test
Comparing 41 hospitalised patients with type 2 diabetes and 44 volunteers, plasma adrenomedullin 2 measured by ELISA was higher in diabetes and tracked body mass index, diastolic pressure, triglycerides, uric acid, glucose and HbA1c. Its best area under the ROC curve was only 0.59, so the authors judged it of no use for diagnosing diabetes.
Lower in dialysis patients, with a link to vessel calcification
Serum adrenomedullin 2 in 116 people on maintenance haemodialysis had a median of about 25 pg/mL, against about 138 pg/mL in 52 matched healthy controls. Within the dialysis group, patients below the median had less abdominal aortic calcification; the authors read the higher levels as a compensatory rise and found the level an independent factor for calcification alongside parathyroid hormone and age.
A prognostic marker in breast cancer
Before surgery, 252 women with breast cancer had higher plasma adrenomedullin 2 than 100 healthy women. Over five years of follow-up, a higher preoperative level independently predicted death, recurrence or metastasis, and shorter disease-free and overall survival.
Rises on tilting in children with postural tachycardia
In 29 children with postural orthostatic tachycardia syndrome and 32 healthy children, the supine level was slightly lower in the patients. In the patients it rose during a head-up tilt test, and the size of the rise correlated with how much the heart rate climbed (r = 0.435). This is an association; the study did not test whether the peptide causes the symptoms.
Relaxes uterine arteries only in pregnancy
Uterine artery segments from nonpregnant women did not relax to CGRP, adrenomedullin or adrenomedullin 2, while segments from pregnant women relaxed to all three, with CGRP the most effective and the other two equal. The arteries carried the CLR-RAMP1 and CLR-RAMP2 receptor pairs; sFLT-1, a factor raised in pre-eclampsia, weakened the receptor's coupling to all three peptides.
Protects human heart muscle cells from simulated ischaemia
Cultured human ventricular heart cells made adrenomedullin 2 and its receptor parts. Added during simulated ischaemia and reoxygenation, the peptide raised cell survival to 59-61% from 39%, an effect lost when the CLR or RAMP2 receptor components were knocked down. Peptide released by co-cultured heart endothelial cells gave the same protection, pointing to a paracrine role.
Lingers on its own receptor
In live-cell assays adrenomedullin 2 bound the CLR-RAMP3 receptor (the AM2 receptor) with an affinity similar to adrenomedullin's but came off much more slowly, so its cAMP signal there lasted longer than any other pairing of the three peptides and three receptors. The slow release mapped to the peptide's middle section and the outer part of RAMP3, making the AM2 receptor its kinetically preferred partner.
Discovered as a new CGRP-family peptide
A genome search identified intermedin as a new member of the calcitonin/CGRP family, expressed mainly in the pituitary and gut. It raised cAMP in cells with CGRP receptors, signalled only when the CLR receptor was paired with a RAMP partner, and, unlike CGRP and adrenomedullin, showed no preference among the three RAMPs. Injected into normal and spontaneously hypertensive rats it lowered blood pressure, and in mice it slowed stomach emptying and reduced food intake.
Lowers pressure in the blood, raises it in the brain
Given intravenously to rats and mice, adrenomedullin 2 lowered blood pressure. It was found in plasma, heart, lung, stomach, kidney, pituitary and brain. Injected into the brain's ventricles of rats it instead raised blood pressure and heart rate for a long time, more than adrenomedullin did, an effect blocked by phentolamine and so driven by the sympathetic nerves; it also cut food and water intake.
Browns fat and improves insulin resistance in obese mice
Its level fell in the fat of mice made obese on a high-fat diet. Delivered by implanted pump, adrenomedullin 2 lowered blood glucose, insulin and free fatty acids and improved insulin sensitivity in a clamp test; mice engineered to make extra peptide in fat gained less weight and burned more energy, with signs of brown-fat-like (beige) changes in white fat.
Protects septic mice; higher levels track survival in patients
In septic mice, adrenomedullin 2 repaired the leaky junctions between blood vessel cells and reduced the influx of inflammatory macrophages, and giving the peptide lessened organ injury and improved survival. In a patient group described in the same paper, people with higher levels had a lower risk of shock, lower severity scores and better survival.
A gut nerve signal that calms intestinal inflammation
Gut (enteric) neurons in mice made adrenomedullin 2, and its receptor on group 2 innate lymphoid cells was needed for their tissue-protective output of amphiregulin; deleting the receptor parts worsened intestinal damage, and recombinant peptide limited inflammation. In people with inflammatory bowel disease, expression of the receptor genes CALCRL and RAMP3 was altered.
Drives breast cancer spread in mice and cells
Adrenomedullin 2 was higher in breast cancer samples and tracked lymph node spread. In cancer cells it boosted growth, migration and invasion through Src kinase and the c-Myc oncogene, and in mice with 4T1 breast tumours a blocking antibody against it slowed tumour growth and reduced lung metastases. The protective effects seen elsewhere are therefore not the whole story.
A counter-regulatory peptide in heart and kidney
This review describes how a longer precursor is cut into active fragments of 53, 47 and 40 amino acids, all sharing the CGRP and adrenomedullin receptors with a distinct potency pattern. The peptide is plentiful in hypothalamus, pituitary and kidney but low in adult plasma, widens systemic and lung vessels, strengthens heart contraction and protects heart muscle in animal models, and its expression rises in stressed hearts.
Its pharmacology still does not quite add up
Discovered in 2004 and widely distributed, adrenomedullin 2 lowers blood pressure when given into the circulation but raises it from inside the brain, increases prolactin release, reduces food intake and alters kidney salt handling in animals. It acts best at the CLR-RAMP3 receptor without being more potent than adrenomedullin anywhere, and some tissue responses survive blockers of every known receptor, so a separate receptor has not been ruled out.
A wide range of disease models
This review gathers work on adrenomedullin 2 in tumours, where it can promote growth and spread, in blood vessel formation, and in protective roles in ischaemia-reperfusion injury, kidney injury, obesity, diabetes, heart failure and sepsis. It notes that how the short active forms are made in the body, and what they signal downstream, is still unclear, and that the work has yet to reach the clinic.
No Established Human Dose
Adrenomedullin 2 has not been given to people in any study we found. The human evidence is measurement only: blood levels in healthy adults and in heart failure, coronary syndromes, diabetes, dialysis and cancer, staining of autopsy tissue, a gene-variant cohort, and experiments on donated human cells and arteries. Every study that administered the peptide used rats, mice or cultured cells, so there is no human amount to report.
What this rests on: PMID 26767798, PMID 16359754, PMID 21832999, PMID 26743504.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Adrenomedullin 2 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Adrenomedullin 2 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Adrenomedullin 2, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Adrenomedullin 2 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Adrenomedullin 2. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Adrenomedullin 2 lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: It lowered blood pressure when given into the circulation of rats and mice (PMIDs 14615490, 15576658); Acting in the brain it raised blood pressure and heart rate in rats (PMID 15576658); In breast cancer cells and mice it promoted tumour growth and spread (PMID 35896852). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Adrenomedullin 2. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No person has been given adrenomedullin 2, so it has no reported side effects in humans”).
Interactions
Unknown: a PubMed search for human interaction studies of Adrenomedullin 2 (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Adrenomedullin 2 products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere: no approval and no treatment trial in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
No person has been given adrenomedullin 2, so it has no reported side effects in humans. The animal and cell findings below point to effects that would matter.
Contraindications & Cautions
There is no product and no human safety data.
Legal Status
Adrenomedullin 2 is a research peptide. It has no approval anywhere and no clinical trial in the sources read.
Frequently Asked Questions
?What is adrenomedullin 2?
A peptide of the calcitonin/CGRP family, discovered in 2004 and also called intermedin. It shares receptors with CGRP and adrenomedullin and is cut from a longer precursor into several active forms.
?Is it the same as adrenomedullin?
No. It is a separate gene and peptide that acts on the same receptor family. It binds the AM2 receptor about as tightly as adrenomedullin but stays bound longer. Adrenomedullin has its own entry.
?Has adrenomedullin 2 been tested in people?
Only measured. Studies have tracked its blood level in heart failure, heart attacks, diabetes, dialysis and cancer, but none has given it to anyone.
?What does it do in animals?
In rodents it lowers blood pressure from the circulation, raises it from inside the brain, reduces food intake, and protected heart, vessels and gut in several disease models. It also helped breast tumours grow in mice.
?Is a high blood level bad?
In heart attack and breast cancer cohorts, higher levels went with worse outcomes, while in sepsis higher levels went with better survival. Assays differ widely, so a number from one lab cannot be read against another study's cutoff.
?Can you buy it?
It is not an approved medicine anywhere and has no human dose. Grey Peptides does not sell or link to any seller.
References
- [pubmed] Bell D, et al. "Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure." Peptides, 2016;76:19-29. PMID: 26767798.
- [pubmed] Takahashi K, et al. "Immunocytochemical localization of adrenomedullin 2/intermedin-like immunoreactivity in human hypothalamus, heart and kidney." Peptides, 2006;27(6):1383-9. PMID: 16359754.
- [pubmed] Hirose T, et al. "Influence of adrenomedullin 2/intermedin gene polymorphism on blood pressure, renal function and silent cerebrovascular lesions in Japanese: the Ohasama study." Hypertens Res, 2011;34(12):1327-32. PMID: 21832999.
- [pubmed] Tang B, et al. "Intermedin as a prognostic factor for major adverse cardiovascular events in patients with ST-segment elevation acute myocardial infarction." Peptides, 2014;58:98-102. PMID: 24969626.
- [pubmed] Li P, et al. "Prognostic Value of Plasma Intermedin Level in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome." Medicine (Baltimore), 2016;95(16):e3422. PMID: 27100434.
- [pubmed] Liu F, et al. "THE INCREASED PLASMA LEVELS OF INTERMEDIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS." Acta Endocrinol (Buchar), 2022;18(3):271-277. PMID: 36699172.
- [pubmed] Bao W, et al. "Compensatory elevated serum intermedin levels are associated with increased vascular calcification in hemodialysis patients." Int Urol Nephrol, 2022;54(11):3001-3007. PMID: 35644015.
- [pubmed] Lu YM, et al. "The prognostic value of intermedin in patients with breast cancer." Dis Markers, 2015;2015:862158. PMID: 25694747.
- [pubmed] Li H, et al. "[Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance]." Zhonghua Er Ke Za Zhi, 2015;53(5):375-8. PMID: 26080669.
- [pubmed] Chauhan M, et al. "Calcitonin Gene Related Peptide, Adrenomedullin, and Adrenomedullin 2 Function in Uterine Artery During Human Pregnancy." Endocrinology, 2022;163(1). PMID: 34558598.
- [pubmed] Bell D, et al. "Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM₁ receptor." Peptides, 2016;76:1-13. PMID: 26743504.
- [pubmed] Babin KM, et al. "Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin(2) G protein-coupled receptor." J Biol Chem, 2023;299(6):104785. PMID: 37146967.
- [pubmed] Roh J, et al. "Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes." J Biol Chem, 2004;279(8):7264-74. PMID: 14615490.
- [pubmed] Taylor MM, et al. "Intermedin/adrenomedullin-2 acts within central nervous system to elevate blood pressure and inhibit food and water intake." Am J Physiol Regul Integr Comp Physiol, 2005;288(4):R919-27. PMID: 15576658.
- [pubmed] Zhang H, et al. "Intermedin/adrenomedullin 2 polypeptide promotes adipose tissue browning and reduces high-fat diet-induced obesity and insulin resistance in mice." Int J Obes (Lond), 2016;40(5):852-60. PMID: 26786353.
- [pubmed] Xiao F, et al. "Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses." Nat Commun, 2018;9(1):2644. PMID: 29980671.
- [pubmed] Uddin J, et al. "CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation." Nat Immunol, 2025;26(9):1516-1526. PMID: 40817416.
- [pubmed] Kong L, et al. "Intermedin (adrenomedullin 2) promotes breast cancer metastasis via Src/c-Myc-mediated ribosome production and protein translation." Breast Cancer Res Treat, 2022;195(2):91-103. PMID: 35896852.
- [review] Bell D, et al. "Intermedin (adrenomedullin-2): a novel counter-regulatory peptide in the cardiovascular and renal systems." Br J Pharmacol, 2008;153 Suppl 1(Suppl 1):S247-62. PMID: 17965749.
- [review] Hong Y, et al. "The pharmacology of adrenomedullin 2/intermedin." Br J Pharmacol, 2012;166(1):110-20. PMID: 21658025.
- [review] Yang Z, et al. "Multi-biological functions of intermedin in diseases." Front Physiol, 2023;14:1233073. PMID: 37745233.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Status comes from Drugs@FDA (openFDA) and EMA's Article 57 product data, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.