Hexarelin is a synthetic hexapeptide growth hormone secretagogue (GHS) and an analog of GHRP-6, developed in the early 1990s as a research tool and investigational agent for growth hormone (GH) deficiency and cardiac indications.12 It is supplied in Canada as a research-use-only (RUO) material; it is not an approved drug and is not authorized for human or veterinary use by Health Canada or any other regulator. Hexarelin reached Phase II trials but was never marketed.1 The summary below reports only what investigators measured in published studies and uses no usage directions. Note that several human findings derive from small studies (often ≤12 subjects), and chronic-dosing data show the GH response attenuates over weeks.56
Sequence & identity
Chemical identity per PubChem CID 6918297 (InChIKey RVWNMGKSNGWLOL-GIIHNPQRSA-N).7 Hexarelin is not a simple linear L-peptide: it contains D-amino acids and a non-coded D-2-methyl-tryptophan residue, with a C-terminal amide.
Mechanisms studied
Researchers report that hexarelin acts as an agonist at the growth hormone secretagogue receptor (GHS-R1a), the same receptor targeted by the endogenous ligand ghrelin, stimulating GH release at both pituitary and hypothalamic levels in animal and human studies.12 The D-2-methyl-tryptophan substitution at position 2 was reported to confer greater resistance to aminopeptidase degradation relative to GHRP-6.2 Separately, investigators observed binding to specific cardiac (myocardial) GHS receptors and proposed that some cardiovascular effects may be GH-independent.3 In vitro work also reported rapid receptor desensitization, with the GH-secretagogue (ghrelin) receptor response declining within minutes of repeated exposure,5 a pattern echoed in human chronic-dosing studies.6
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| Imbimbo et al., Eur J Clin Pharmacol 1994 (PMID 7957536) | Single intravenous boluses of 0.5, 1, and 2 µg/kg in 12 healthy adult men | As reported in a double-blind, placebo-controlled rising-dose study; peak GH rose dose-dependently (≈0.5 µg/kg 26.9, 1 µg/kg 52.3, 2 µg/kg 55.0 ng/mL vs placebo 3.9). RUO research parameters only — not a usage recommendation.4 |
| Ghigo et al., J Clin Endocrinol Metab 1994 (PMID 8126144) | IV 1–2 µg/kg, subcutaneous 1.5–3 µg/kg, intranasal 20 µg/kg, and oral 20–40 mg in healthy young volunteers | Reported as a multi-route bioavailability study in 12 healthy young volunteers; all routes elicited GH release, with parenteral routes substantially more potent than intranasal or oral. Reported research parameters, not directions for use.2 |
| Bisi et al., J Endocrinol Invest 1999 (PMID 10342360) | Single IV administration in 7 healthy men (cardiac-function study) | Used to assess acute cardiovascular effects by radionuclide angiocardiography; exact mg/kg not specified in the abstract. Reported research context only.3 |
| Tivesten et al., Endocrinology 2000 (PMID 10614623) — animal | Subcutaneous 10 or 100 µg/kg/day, twice daily for 2 weeks in post-myocardial-infarction rats | Animal model dosing; not applicable to humans. The higher dose (100 µg/kg/day) decreased total peripheral resistance and increased stroke volume and cardiac output.8 |
Effects observed in research
In healthy human volunteers, studies reported that intravenous hexarelin produced a rapid, dose-dependent rise in circulating GH, with peak concentrations roughly 7- to 14-fold over placebo at 0.5–2 µg/kg and GH peaking near 15–30 minutes.4 In a small study of 7 men, investigators observed that a single dose increased left ventricular ejection fraction (64.0 ± 1.5% to 70.7 ± 3.0%, p<0.03) without significant changes in mean blood pressure or heart rate, while raising GH to an extent similar to recombinant human GH; the authors described this short-lasting positive inotropic effect as seemingly GH-independent and possibly mediated by myocardial GHS receptors.3 In post-myocardial-infarction rats, researchers reported that hexarelin improved cardiac function and decreased peripheral resistance to a degree comparable to exogenous GH.8 Studies also reported that the GH response is blunted in elderly versus young subjects9 and that it attenuates progressively with repeated dosing — though one long-term human study found the attenuation was partial and reversible after a washout period.6
Strength of evidence
Evidence grade B. Human data exist but are limited: several short-term, small (often ≤12 subjects) studies in healthy volunteers and patients reported GH-releasing and acute cardiovascular effects,234 and the compound reached Phase II trials for GH deficiency and congestive heart failure but was discontinued and never marketed.1 Cardiac-remodeling and longer-term efficacy claims rest largely on animal models.8 A consistent, well-replicated limitation is desensitization: in vitro work showed rapid GHS-R1a desensitization,5 and long-term human dosing produced a progressive (partial, reversible) decline in GH response.6 No modern large-scale randomized clinical trials establish safety or efficacy for any indication. Pharmacokinetic parameters reported in secondary sources (e.g., plasma half-life on the order of tens of minutes) are not robustly established in the peer-reviewed human literature and should be treated as limited published data.
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
References
- Examorelin (hexarelin) reached Phase II clinical development for growth hormone deficiency and congestive heart failure (developed by Mediolanum Farmaceutici) and was discontinued without being marketed. See Examorelin overview, Wikipedia (citing the drug’s development history); and Ishida J, et al. Growth hormone secretagogues: history, mechanism of action, and clinical development. JCSM Rapid Commun. 2020;3(1):25-37.
- Ghigo E, Arvat E, Gianotti L, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. J Clin Endocrinol Metab. 1994;78(3):693-698. PMID 8126144.
- Bisi G, Podio V, Valetto MR, Broglio F, et al. Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest. 1999;22(4):266-272. PMID 10342360.
- Imbimbo BP, Mant T, Edwards M, Amin D, Dalton N, Boutignon F, Lenaerts V, Wüthrich P, Deghenghi R. Growth hormone-releasing activity of hexarelin in humans. A dose-response study. Eur J Clin Pharmacol. 1994;46(5):421-425. PMID 7957536.
- Orkin RD, New DI, Norman D, Chew SL, Clark AJL, Grossman AB, Korbonits M. Rapid desensitisation of the GH secretagogue (ghrelin) receptor to hexarelin in vitro. J Endocrinol Invest. 2003;26(8):743-747. PMID 14669829.
- Rahim A, O’Neill PA, Shalet SM. Growth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab. 1998;83(5):1644-1649. PMID 9589671 (16 weeks twice-daily SC hexarelin 1.5 µg/kg; attenuation of GH response partial and reversible after a 4-week washout).
- National Center for Biotechnology Information. PubChem Compound Summary for CID 6918297, Hexarelin (Examorelin). InChIKey RVWNMGKSNGWLOL-GIIHNPQRSA-N; MF C47H58N12O6; MW 887.0; CAS 140703-51-1.
- Tivesten A, Bollano E, Caidahl K, et al. The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology. 2000;141(1):60-66. PMID 10614623.
- Arvat E, Gianotti L, Grottoli S, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F, Ghigo E. Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects. J Clin Endocrinol Metab. 1994;79(5):1440-1443. PMID 7962341.