Intermedin
Also known as: Adrenomedullin 2, AM2, IMD, intermedin-53, intermedin-47, ADM2, IMD1-53
Endogenous peptide hormone; calcitonin gene-related peptide (CGRP) superfamily / calcitonin/adrenomedullin family
What it is
Intermedin is a naturally occurring peptide hormone that researchers are studying for its protective roles in the heart, kidneys, and blood vessels. It belongs to the same family as CGRP and adrenomedullin. No approved therapeutic formulation exists; current interest is largely confined to laboratory and preclinical research.
The scientific side
intermedin (IMD) is an endogenous peptide belonging to the CGRP/calcitonin superfamily. Its primary receptors are heterodimeric complexes formed between the class B G-protein-coupled receptor CLR (calcitonin receptor-like receptor) and one of three receptor activity-modifying proteins: RAMP1, RAMP2, or RAMP3. Research reported in the Journal of Biological Chemistry (PMID 37146967) established that IMD is kinetically selective for the CLR-RAMP3 complex (the AM2 receptor), binding with a markedly slow off-rate and producing substantially longer-duration cAMP signaling compared to adrenomedullin or CGRP at the same receptor. Subsequent work (PMID 38670438) confirmed that IMD fragments such as IMD(8-47) and IMD-53 display even more prolonged cAMP signaling, up to 8-fold longer-acting than adrenomedullin at CLR-RAMP3. Downstream signaling branches activated by IMD include cAMP/PKA, PI3K/Akt, AMPK, and MAPK pathways depending on cell type and context. In cardiomyocytes (PMID 39817339), IMD signals through RAMP2 and activates MAPK to regulate genes involved in glycolysis, beta-oxidation, and oxidative phosphorylation. In renal tubular epithelial cells (PMID 42710697), IMD activates AMPK and suppresses HIF-1alpha, rebalancing fatty acid oxidation versus glycolysis. In vascular endothelial cells (PMID 40228707), IMD activates the AMPK/GTPCH-I/BH4 axis to inhibit eNOS uncoupling and reduce reactive oxygen species. In cardiomyocytes under pressure overload, IMD1-53 upregulates mitochondrial SIRT3, which deacetylates and activates SOD2, reducing oxidative stress (PMID 40602647). IMD also inhibits NF-kappaB-driven inflammatory cascades in cardiac tissue after kidney ischemia-reperfusion injury (PMID 41526164) and promotes T- and B-cell proliferation through ERK1/2 phosphorylation during sepsis (PMID 37352568). In the intestine, enteric-neuron-derived ADM2 acts on ILC2 cells through CLR/RAMP3 receptor subunits to drive amphiregulin production and tissue-protective responses (PMID 40817416). Collectively, IMD exerts pleiotropic cytoprotective effects across cardiac, renal, vascular, immune, and neural compartments primarily via sustained cAMP generation and AMPK-mediated antioxidant signaling.
Class: Endogenous peptide hormone; calcitonin gene-related peptide (CGRP) superfamily / calcitonin/adrenomedullin family
Administration & storage
- Administration
- Subcutaneous continuous infusion via osmotic mini-pump (mouse studiesPMID 40602647)Intraperitoneal bolus injection (rat studiesPMID 36836072)Intravenous infusion in cell-culture perfusion and ex vivo vascular models
- Storage
- No human-use storage guidance available from the reviewed abstracts. Synthetic peptide research reagents are typically stored lyophilized at -20°C and reconstituted immediately before use.
Legal & regulatory status
Not approved as a drug. No IND or NDA on record. Research reagent only.
Not specifically listed on the WADA Prohibited List. No anti-doping status confirmed in the reviewed abstracts.
Not approved as a therapeutic agent. No regulatory filing identified.
What it's studied for
- Cardiac protection and age-related cardiac remodeling Preclinical (animal models)
- Acute kidney injury and AKI-to-CKD transition prevention Preclinical (animal and cell models)
- Contrast-induced acute kidney injury (CIAKI) Preclinical (rat model and cell culture)
- Diabetic cardiomyopathy Preclinical (rat and mouse models)
- Atherosclerosis and vascular endothelial protection Preclinical (apoE-knockout mouse model)
- Atrial fibrillation prevention via antifibrotic action Preclinical (rat heart failure model)
- Sepsis and immune modulation Preclinical (cecal ligation and puncture mouse model)
- Intestinal inflammation and ILC2-mediated tissue protection Preclinical (mouse model) with human correlation data
- Non-alcoholic fatty liver disease (NAFLD) Preclinical (mouse model)
- Anxiety and blood-brain barrier integrity Preclinical (mouse knockout model)
- Vascular smooth muscle cell senescence and aging vasculature Preclinical (mouse model)
- Acute heart failure following acute kidney injury Preclinical (mouse model)
- Neovascular age-related macular degeneration (AMD) Preclinical (laser-induced choroidal neovascularization mouse model)
Safety signals
- Hypotension risk — potent vasodilator activity
- Proangiogenic activity — potential tumor-promoting effects in cancer contexts
- Immunomodulatory effects — potential for unintended immune activation or suppression
- Blood-brain barrier modulation
- Interaction with CGRP receptor signaling — possible interference with anti-migraine therapies
- No human safety data — entirely preclinical compound
- Prolonged receptor residence time — potential for sustained off-target signaling
- Potential effects on pregnancy — vascular and metabolic role confirmed in knockout mouse studies
All studies (11)
Frequently asked
Is intermedin the same as adrenomedullin?
Intermedin (also called adrenomedullin 2 or AM2) is a related but distinct peptide from adrenomedullin (AM). Both belong to the CGRP/calcitonin superfamily and share receptor components (CLR plus RAMPs), but intermedin is encoded by a separate gene (ADM2) and has a distinct receptor preference. Research described in PMID 37146967 found that intermedin preferentially binds the CLR-RAMP3 receptor with a slower off-rate and longer-lasting signaling than adrenomedullin, which prefers CLR-RAMP2.
Has intermedin been tested in human clinical trials?
As of the reviewed literature, no interventional human clinical trials of exogenous intermedin administration have been completed or published. The one study registered on ClinicalTrials.gov (NCT00133783) was an observational cross-sectional study measuring plasma intermedin levels in women across reproductive stages — not a drug administration study. Intermedin remains a preclinical research compound.
What diseases is intermedin being studied for?
Based on the reviewed abstracts, the main preclinical research areas for intermedin include: protection against acute and chronic kidney injury, diabetic cardiomyopathy, aging-associated cardiac remodeling, atherosclerosis, atrial fibrillation, non-alcoholic fatty liver disease, sepsis-related immune dysfunction, intestinal inflammation, and anxiety/blood-brain barrier integrity. All findings are from animal models or cell studies; no efficacy data in humans have been published.
Can intermedin be purchased and self-administered?
Intermedin is sold as a research-grade synthetic peptide by biochemical reagent suppliers for laboratory use only. There is no approved pharmaceutical formulation, no established safe human dose, and no clinical safety data. The reviewed research abstracts do not describe or support any protocol for self-administration in humans.
Does intermedin affect blood pressure?
Preclinical and observational data suggest intermedin has vasodilatory and blood-pressure-lowering properties. The ClinicalTrials.gov study NCT00133783 at Chang Gung Memorial Hospital was designed in part around observations of dose-dependent blood pressure suppression in rats after intraperitoneal intermedin. AM2-knockout mice showed elevated blood pressure during pregnancy (PMID 36875025). The magnitude of blood pressure effects in humans from exogenous intermedin has not been measured in any published study.