Hexarelin

Hexarelin (also called Examorelin, sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂) is a synthetic hexapeptide GHRP developed in the 1990s as a more potent successor to GHRP-6. It binds the growth hormone secretagogue receptor 1a (GHS-R1a / ghrelin receptor) and triggers growth-hormone release from the pituitary. It retains some of the off-target effects on cortisol and prolactin that the later-generation Ipamorelin eliminated.

Overview

Hexarelin was developed by Mediolanum Farmaceutici in Italy and tested in clinical trials through the late 1990s for short stature and GH deficiency. It never received FDA approval; the parallel development of recombinant human growth hormone and the longer-acting CJC-1295 / Ipamorelin generation displaced it from commercial development.

The peptide is roughly 2 to 3 times more potent than GHRP-6 at the ghrelin receptor in published binding assays. Like other GHRPs, repeated bolus dosing produces desensitization over weeks of continuous use.

Mechanism

GHS-R1a (ghrelin receptor) agonism in pituitary somatotrophs:

• GH release. Direct activation of GHS-R1a in the anterior pituitary produces a robust GH pulse. The pulse is synergistic when combined with a GHRH analog like CJC-1295.
• Cortisol + prolactin spike. Off-target activation drives modest transient cortisol and prolactin elevations, larger than with the more-selective Ipamorelin.
• Cardioprotection (research signal). Hexarelin produces ghrelin-receptor-independent cardioprotective effects in rodent ischemia-reperfusion models. See: Locatelli V, et al. Circulation. 1999.
• Appetite stimulation. Indirect ghrelin-axis effects on hypothalamic AgRP neurons increase food intake.

See: Ghrelin_receptor, GHRP-6, Growth_hormone.

Evidence

Key publications:

• Imbimbo BP, Mant T, Edwards M, et al. "Growth hormone-releasing activity of hexarelin in humans. A dose-response study." Eur J Clin Pharmacol. 1994;46(5):421-5. [PMID 7957535](https://pubmed.ncbi.nlm.nih.gov/7957535/).
• Locatelli V, Rossoni G, Schweiger F, et al. "Growth hormone-independent cardioprotective effects of hexarelin in the rat." Endocrinology. 1999;140(9):4024-31. [PMID 10465272](https://pubmed.ncbi.nlm.nih.gov/10465272/).

Pharmacokinetics

Plasma half-life is approximately 70 minutes after subcutaneous injection. GH-release peak occurs 30 to 60 minutes post-dose. Tachyphylaxis develops with chronic daily dosing as GHS-R1a downregulates.

Dosing literature

Historical Phase 1/2 trials used 0.1 to 2 mcg/kg subcutaneously twice daily. This wiki does not recommend any human dose. Hexarelin is supplied as a research-grade chemical reference compound for in-vitro use only.

Storage

Lyophilized: 2 to 8 °C, stable 12+ months. Reconstituted: 2 to 8 °C, use within 14 days. See Reconstitution.

Regulatory status

• United States. Not FDA-approved. Investigational / research-only.
• WADA. Prohibited at all times under category S2 (peptide hormones, growth factors). Hexarelin is detectable on standard WADA-accredited screens.

Side effects (from historical clinical literature)

• Transient cortisol elevation (smaller than GHRP-6, larger than ipamorelin)
• Transient prolactin elevation
• Tachyphylaxis (reduced GH response) on chronic daily dosing
• Mild flushing and nausea at higher doses

See also

• Ipamorelin · selective GHS-R1a agonist with cleaner profile
• GHRP-6 · predecessor in the GHRP family
• CJC-1295 · GHRH analog often paired with GHRPs
• Ghrelin_receptor
• Growth_hormone

References

• Imbimbo BP, et al. Eur J Clin Pharmacol 1994. [PMID 7957535](https://pubmed.ncbi.nlm.nih.gov/7957535/)
• Locatelli V, et al. Endocrinology 1999. [PMID 10465272](https://pubmed.ncbi.nlm.nih.gov/10465272/)