D tier · weak
It has more long-term human data than most compounds here, and that data is unfavourable: the GH response attenuates progressively over 16 weeks and IGF-1 did not change at all across 20 weeks of treatment.
hexarelin
Hexarelin is a synthetic hexapeptide agonist of the ghrelin receptor (GHS-R1a) that acutely raises growth hormone along with prolactin, ACTH and cortisol. It reached phase 2 trials for growth hormone deficiency and congestive heart failure but was never marketed, and controlled studies show the GH response desensitises substantially with continued administration.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade D above is our own and is not adjusted because we stock it.
the explanation
Hexarelin is a six-amino-acid peptide that copies the hunger hormone ghrelin and causes a large burst of growth hormone, but it also raises stress hormones and prolactin at the same time. The bigger problem is that the body adapts: over 16 weeks the growth hormone response shrank progressively and IGF-1 never rose at all.
regulatory status
Not approved; development abandoned
Reached phase 2 trials for growth hormone deficiency and congestive heart failure but did not complete development and was never marketed in any jurisdiction.
how it works · proposed mechanism
Hexarelin does two separate things: it triggers growth hormone at the pituitary and it acts directly on heart tissue through a different receptor.
Ghrelin receptor agonist
Hexarelin binds GHS-R1a on pituitary somatotrophs and produces a large acute GH pulse. It is not selective for GH the way ipamorelin is, and simultaneously stimulates prolactin, ACTH and cortisol.
Direct cardiac activity via CD36
Hexarelin has GH-independent cardiotropic effects demonstrated in patients with severe left ventricular dysfunction, mediated substantially through the scavenger receptor CD36 rather than GHS-R1a. This drove a phase 2 programme in cardiomyopathy.
The receptor desensitises
Rahim 1998 gave 1.5 µg/kg twice daily for 16 weeks and found the area under the GH curve fell significantly by week 4 and again by week 16, recovering 4 weeks after stopping. Tolerance to the GH effect is the central pharmacological problem.
IGF-1 never moved
Across the same 20-week study, serum IGF-1 and IGF binding protein-3 did not change significantly. The authors concluded that the biological impact of chronic hexarelin on the GH-IGF-1 axis appears minimal.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Chronic dosing produces progressive tachyphylaxis, with reported reductions of 50-75% in GH-releasing efficacy over weeks to months, and in the best long-term study IGF-1 and IGFBP-3 did not move at all across 20 weeks, meaning the downstream anabolic signal never materialised. Acutely it is also non-selective, raising prolactin, ACTH and cortisol dose-dependently, and the one 16-week study finding no pituitary-adrenal overstimulation used a low dose of 1.5 µg/kg twice daily rather than the higher exposures typical outside research.
key published findings
- Human study (Rahim, JCEM 1998, 83:1644-9): 1.5 µg/kg subcutaneously twice daily for 16 weeks caused the mean area under the GH curve to decrease significantly at both week 4 and week 16 versus baseline, with recovery 4 weeks after cessation, while serum IGF-1 and IGFBP-3 did not change significantly across the 20-week period.
- Human study (Rahim, Clinical Endocrinology 1999): across the same 16-week twice-daily protocol, urinary free cortisol, basal cortisol and area under the ACTH curve showed no significant change and prolactin was unchanged, leading the authors to conclude that chronic hexarelin at this dose did not overstimulate the pituitary-adrenal axis, in contrast to acute administration.
- Human study (Arvat, European Journal of Endocrinology 1997, n=60 across four age groups): 2.0 µg/kg IV hexarelin raised prolactin similarly in prepubertal children, pubertal children, young adults and elderly subjects; the GH response peaked in pubertal and young adults and declined significantly in the elderly, while ACTH rose during puberty and cortisol showed no significant age-related difference.
- Human study (Laron, Clinical Endocrinology 1995, n=8 prepubertal short children aged 4-11.6): intranasal hexarelin 60 µg/kg three times daily for up to 8 months raised IGF-1 and increased mean linear growth velocity from 5.3 ± 0.8 to 8.3 ± 1.7 cm/year, with decreased skinfold thickness.
- Human study (Imazio, European Journal of Heart Failure 2002): hexarelin produced GH-independent cardiotropic activity in patients with severe left ventricular dysfunction from dilated and ischaemic cardiomyopathy, supporting a CD36-mediated direct cardiac mechanism separate from its pituitary action.
limitations of the evidence
- No published human pharmacokinetic study establishes an elimination half-life; duration is inferred from GH response curves rather than measured plasma concentrations.
- The paediatric growth data come from 8 uncontrolled subjects with familial short stature, not a randomised trial, and no final-height outcome was reported.
- The cardiac work is mechanistically interesting but consists of small acute-administration studies; no controlled trial has tested clinical cardiac outcomes.
identity
| full name | His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2, a synthetic growth hormone-releasing hexapeptide |
| category | Growth Hormone |
| modality | peptide |
| formula | C47H58N12O6 |
| molar mass | 887.05 g/mol |
| cas | 140703-51-1 |
| half-life | Not well characterised in published human PK; IV GH peak at 15-30 min, intranasal at 30-60 min |
| sequence | His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2 |
laboratory handling
| storage | Lyophilised hexarelin is stored at -20°C, desiccated and protected from light, for long-term laboratory storage. Reconstituted solution is held at 2-8°C for short-term use and aliquoted before freezing to avoid repeated freeze-thaw cycles. |
| solubility | Reported laboratory solubility is approximately 10 mg/mL in PBS pH 7.2, 30 mg/mL in DMSO or DMF and 5 mg/mL in ethanol; aqueous buffer or bacteriostatic water is the usual reconstitution solvent. |
| co-studied with | Hexarelin is a GHS-R1a agonist and belongs to the GHRP arm of the GHRH-plus-GHRP co-study logic, but its documented tachyphylaxis means the combination rationale that applies to shorter-exposure GHRPs has not been demonstrated to hold for it over time. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedJournal of Clinical Endocrinology & Metabolism · 1998 · peer-reviewed
Clinical Endocrinology · 1999 · peer-reviewed
European Journal of Endocrinology · 1997 · peer-reviewed
Clinical Endocrinology · 1995 · peer-reviewed
European Journal of Heart Failure · 2002 · peer-reviewed
others in Growth Hormone