Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Hexarelin — also called examorelin — is a synthetic hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂) that activates the growth hormone secretagogue receptor (GHSR-1a). It is a close analog of GHRP-6, with a methyl substitution on the second tryptophan residue that increases potency and metabolic stability. Like other GHSR-1a agonists, it has been investigated for both growth hormone release and a separate cluster of cardiovascular effects mediated through the CD36 receptor.
History
Hexarelin was developed in the early 1990s by Mediolanum Farmaceutici in Italy and licensed to Pharmacia & Upjohn. The 1994 Ghigo et al. paper in the Journal of Clinical Endocrinology & Metabolism characterized its activity in humans across intravenous, subcutaneous, intranasal, and oral routes, demonstrating dose-dependent GH release at each.
Pharmacia & Upjohn advanced hexarelin into Phase II clinical trials for growth hormone deficiency in children and adults. A subcutaneous formulation was studied at 60 mcg/kg twice daily; while it reliably released GH acutely, repeated dosing produced tachyphylaxis (a progressive blunting of the response), and the program did not advance to Phase III.
Following the discovery of ghrelin in 1999 and the identification of CD36 as a secondary receptor for hexarelin, research interest shifted to its possible cardioprotective effects. Several preclinical and small clinical studies in cardiac ischemia and heart failure have been published, but none has reached regulatory approval.
Regulatory status
Hexarelin has no approved medical use in any major jurisdiction. The FDA has not approved it; it is not on the 503A bulk substances list and compounding for patients is not permitted in the United States. The European Medicines Agency has not authorized it.
The World Anti-Doping Agency lists hexarelin under class S2 of the Prohibited List (peptide hormones, growth factors, related substances, and mimetics) — banned in and out of competition. Hexarelin has been detected in multiple anti-doping cases.
Mechanism
Published mechanism papers describe two distinct receptor activities for hexarelin:
- GHSR-1a (ghrelin receptor) — on pituitary somatotrophs and hypothalamic neurons. Activation stimulates phospholipase C signaling, raises intracellular calcium, and triggers a growth hormone pulse. Like GHRP-6, the response is amplified by endogenous GHRH and blunted when GHRH is blocked.
- CD36 — a scavenger receptor expressed on cardiomyocytes, endothelium, and macrophages. Hexarelin binds CD36 and produces effects on cardiac function, lipid handling, and inflammation that are independent of GH release.
The CD36 activity is the basis of the cardiac research interest. In preclinical models, hexarelin reduces ischemia-reperfusion injury and improves left ventricular function — effects that persist even in GH-deficient animals.
Half-life and dosing intervals
The published plasma half-life of hexarelin is approximately 55 to 75 minutes after subcutaneous injection. Intranasal and oral routes show lower bioavailability but produce measurable GH responses at higher doses, as documented in the Ghigo 1994 paper.
In published clinical work, intravenous doses of 1 to 2 mcg/kg produced peak GH responses; subcutaneous doses of 1.5 to 2 mcg/kg produced similar effects with a slower time course. In the Phase II GHD program, 60 mcg/kg twice daily subcutaneously was the tested regimen.
Tachyphylaxis is a documented feature of repeated hexarelin dosing — the GH response diminishes substantially over days to weeks of continuous administration, which is one reason the Phase II program did not advance.
Reconstitution example
Hexarelin is sold lyophilized in 2 mg or 5 mg vials. A 2 mg vial reconstituted with 2 mL of bacteriostatic water yields 1 mg/mL — on a 1 mL U-100 insulin syringe, 10 units (0.1 mL) contains 100 mcg.
A 5 mg vial reconstituted with 2 mL of bacteriostatic water yields 2.5 mg/mL — the same 10-unit mark contains 250 mcg. Vial's calculator handles the unit-to-microgram conversion automatically.
What to know
- Tachyphylaxis. The GH response to hexarelin diminishes substantially with repeated dosing, which limited its clinical development.
- Not approved. No regulator has authorized hexarelin for therapeutic use, and compounding pharmacies in the United States cannot prepare it for patients.
- WADA banned. Use is prohibited in competitive sport.
- CD36 activity. Unlike most other GHSR-1a agonists, hexarelin has documented activity at the CD36 scavenger receptor, which is the basis of ongoing cardiovascular research interest.
- Reported side effects in published trials and observational use include increased hunger, transient flushing, modest cortisol and prolactin elevation, and injection-site reactions. Long-term safety has not been characterized.
- Storage. Lyophilized vials are best stored refrigerated. Once reconstituted, refrigerate and use within 4 weeks per typical supplier stability data.
Sources
- 1.Ghigo E et al. (1994). Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. Journal of Clinical Endocrinology & Metabolism.
- 2.Arvat E et al. (1994). Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects. Journal of Clinical Endocrinology & Metabolism.
- 3.Ghigo E et al. (1997). Growth hormone-releasing peptides. European Journal of Endocrinology.
- 4.Sigalos JT, Pastuszak AW (2018). The Safety and Efficacy of Growth Hormone Secretagogues. Sexual Medicine Reviews.
- 5.World Anti-Doping Agency — Prohibited List (S2).