Hexarelin

Also known as: Examorelin, EP-23905

**Mechanism of Action** Hexarelin (Examorelin, EP-23905) is a synthetic hexapeptide belonging to the growth hormone-releasing peptide (GHRP) family. It acts as a potent agonist at the ghrelin/growth hormone secretagogue receptor (GHS-R1a), stimulating growth hormone (GH) release from the pituitary. However, its cardioprotective effects are largely independent of GH secretion, mediated through direct binding to GHS-R1a and possibly CD36 receptors in cardiac and vascular tissues. This activates intracellular signaling pathways (e.g., PI3K/Akt, MAPK/ERK) that reduce apoptosis, oxidative stress, and inflammation, while improving myocardial contractility and endothelial function. **Key Research Findings** Clinical trials have demonstrated Hexarelin’s ability to improve left ventricular ejection fraction and reduce infarct size in models of ischemia-reperfusion injury. Studies also show enhanced cardiac output and reduced fibrosis in chronic heart failure models, with effects observed even in GH-deficient states. Additionally, Hexarelin exhibits anti-atherosclerotic properties by inhibiting vascular smooth muscle cell proliferation and improving lipid profiles. Its GH-releasing activity is more prolonged than that of natural ghrelin, but tachyphylaxis with repeated dosing has been noted. **Clinical Relevance** Hexarelin is under investigation for acute myocardial infarction, chronic heart failure, and metabolic disorders such as cachexia. Its dual GH-dependent and independent actions offer potential advantages over traditional GH therapy, particularly in patients with GH resistance. However, long-term safety data remain limited, and concerns about GH-related side effects (e.g., insulin resistance, fluid retention) persist. Further trials are needed to establish optimal dosing and therapeutic windows. For research purposes only — not medical advice.

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