Hexarelin Acetate

Hexarelin is a synthetic growth hormone-releasing peptide (GHRP), a six-residue chain that makes the pituitary release growth hormone (GH). A 1994 rat study describes it as a GHRP analog in which tryptophan was replaced by the chemically more stable 2-methyl-tryptophan (Deghenghi et al., 1994), and a 1997 human study calls it a super-analog of GHRP-6 (Arvat et al., 1997).

It acts at the growth hormone secretagogue receptor, GHS-R1a, the receptor for ghrelin (Orkin et al., 2003), and also binds CD36, which its coronary effect in perfused hearts requires (Bodart et al., 2002).

Its formula and 887.04 g/mol describe the free peptide and match PubChem CID 6918297 (887.0 g/mol), the source of the aliases, sequence and CAS number. PubChem records the 1:1 acetate salt as C₄₉H₆₂N₁₂O₈, 947.1 g/mol (CID 88325556).

Published work on hexarelin falls into five areas; each summary names its model. Of roughly 300 PubMed records (October 2026), those tagged as clinical trials all date from 1994 to 2004.

Origin and GH release in rats

In conscious 10-day-old rats, hexarelin strongly stimulated GH secretion. In anesthetized adult male rats, intravenous hexarelin and GHRP-6 released GH with peaks within 10 minutes and similar effectiveness at every amount tested, and subcutaneous hexarelin gave a long-lasting release slightly larger than GHRP-6 (Deghenghi et al., 1994).

In a follow-up, 3 to 10 days of repeated hexarelin enhanced later GH responses in pups but not in adult rats, and in vitro its effect was transient. The authors proposed a minor direct pituitary action, GHRH release in adult rats, and an unknown hypothalamic factor acting together with GHRH (Torsello et al., 1996). Models: infant and adult rats.

Two binding sites: GHS-R1a and CD36

Merck scientists found a high-affinity site in pig and rat anterior pituitary membranes shared by hexarelin, GHRP-6 and two non-peptides, MK-0677 and L-692,429. Binding affinity tracked GH-releasing activity, and GHRH and somatostatin did not displace it (Pong et al., 1996). In human hypothalamic and pituitary membranes, radioiodinated Tyr-Ala-hexarelin bound with nanomolar affinity and was displaced by hexarelin, GHRP-2, GHRP-6 and MK-0677 (Muccioli et al., 1998).

In the heart, photoaffinity labeling found an 84 kDa protein whose N-terminal sequence matched CD36, a glycoprotein on cardiomyocytes and microvascular endothelial cells. Hexarelin raised coronary perfusion pressure in perfused hearts, but not in hearts from CD36-null mice or from spontaneously hypertensive rats lacking CD36 (Bodart et al., 2002). Cross-linking placed the binding site within CD36 residues Asn132 to Glu177, a region overlapping the binding domain for oxidized LDL (Demers et al., 2004). Models: pig, rat and human membranes, perfused rat and mouse hearts.

Hormone release in human studies

In 12 healthy young volunteers, hexarelin released GH by the intravenous, subcutaneous, intranasal and oral routes. The intravenous response was about twice that to the same amount of GHRH, and bioavailability estimated from the GH response was about 77% subcutaneous, 5% intranasal and 0.3% oral (Ghigo et al., 1994).

In six young adults, hexarelin and GHRP-2 gave similar, strong GH responses, larger than after GHRH, and both raised prolactin, ACTH and cortisol, the last two about as much as human corticotropin-releasing hormone did. The authors called both peptides not fully specific (Arvat et al., 1997). Models: healthy young adults.

Desensitization with repeated exposure

In Chinese hamster ovary cells expressing human GHS-R1a, hexarelin raised intracellular calcium, and the response was markedly desensitized 2 to 5 minutes after a first exposure (Orkin et al., 2003). In conscious male rats, a second bolus 2 hours after the first released significantly less GH, though a third did not differ significantly from the first. During continuous infusions of 6 to 174 hours, GH peaked within 40 minutes and returned to basal levels, pulsatile release matched saline controls, and only the longest infusion raised IGF-I (Conley et al., 1998).

In healthy elderly volunteers who received repeated hexarelin for 16 weeks, the GH response to a test exposure fell to about 55% of baseline and returned to baseline 4 weeks after the course ended, while serum IGF-I did not change significantly. The authors called the attenuation partial and reversible (Rahim et al., 1998). Models: transfected cells, rats, healthy elderly volunteers.

Heart models

In hypophysectomized rats, 7 days of hexarelin prevented the worsening of ischemia-reperfusion damage in their explanted hearts, including rises in end-diastolic pressure, coronary perfusion pressure and creatine kinase release. GH did the same, while EP 51389, a GHRP that does not bind the heart, did not (Locatelli et al., 1999). In male ghrelin-knockout mice after coronary artery ligation, 2 weeks of hexarelin or ghrelin lowered mortality (6.7% and 14.3%, against 50% with vehicle), and hexarelin outdid ghrelin on ejection fraction (Mao et al., 2013).

In people, hexarelin raised left ventricular ejection fraction in seven men with GH deficiency, who released almost no GH, and in nine control men, without changes in blood pressure, catecholamines or cardiac output. The authors read the short-lasting effect as probably independent of GH (Bisi et al., 1999). Models: rat hearts, mice, adult men.