NOT FOR HUMAN CONSUMPTION

Hexarelin is a synthetic growth-hormone secretagogue (GHS) and ghrelin-receptor (GHSR-1a) agonist from the GHRP family (hexapeptide). It provokes rapid, pulsatile GH release from pituitary somatotrophs and acts within the hypothalamus. Beyond GHSR-1a, hexarelin also interacts with CD36 on cardiovascular and immune cells, supporting GH-independent cardioprotective effects described in preclinical models. It is not FDA/EMA-approved for therapy; research and compounded use exist in some markets.

Additional Benefits of Hexarelin Now Under Investigation

Benefit	Key take-aways
1 Physiologic GH pulsatility	SC or intranasal hexarelin elicits brief GH peaks and modest IGF-1 rises while preserving hypothalamic–pituitary feedback; synergy with GHRH is well documented. <br/><em>Journal of Clinical Endocrinology & Metabolism; Neuroendocrinology</em>
2 Cardioprotection (I/R and pressure overload)	In rodent infarction and pressure-overload models, hexarelin reduces infarct size, improves LVEF, and limits apoptosis, effects partially independent of GH/IGF-1 and linked to CD36–PI3K–Akt–eNOS signalling. <br/><em>Circulation Research; Cardiovascular Research</em>
3 Anti-fibrotic cardiac remodelling	Chronic dosing attenuates myocardial fibrosis and hypertrophy markers (e.g., collagen I/III, TGF-β), improving diastolic indices. <br/><em>Journal of Molecular and Cellular Cardiology; American Journal of Physiology–Heart</em>
4 Appetite & body-composition in cachexia	As a ghrelin mimetic, hexarelin increases hunger and caloric intake; small studies and models show lean-mass preservation/gain under catabolic conditions. <br/><em>Clinical Nutrition; Annals of Oncology</em>
5 Anti-atrophy in skeletal muscle	Hind-limb unloading and denervation models demonstrate preserved fibre CSA and higher myofibrillar protein synthesis, via GH/IGF-1 plus local GHSR effects. <br/><em>Muscle & Nerve; American Journal of Physiology–Endocrinology</em>
6 Bone-turnover support	Ovariectomised-rat data show ↑ osteocalcin/alkaline phosphatase and modest BMD gains, consistent with GH/IGF-1-mediated anabolism. <br/><em>Bone; Journal of Endocrinology</em>
7 Sleep-architecture enhancement	Bedtime administration augments slow-wave sleep (SWS) and nocturnal GH pulses, with exploratory improvements in next-day cognition. <br/><em>Sleep; Psychoneuroendocrinology</em>
8 GI mucosal protection/healing	GHSR activation promotes angiogenesis and anti-apoptosis in gastric/colonic injury models, accelerating ulcer closure. <br/><em>Gut; American Journal of Pathology</em>
9 Endothelial function & perfusion	Acute dosing enhances endothelium-dependent vasodilation and microvascular perfusion in preclinical systems, aligning with eNOS activation. <br/><em>Vascular Pharmacology; Atherosclerosis</em>

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

Hexarelin binds GHSR-1a (GPCR) on hypothalamic neurons and pituitary somatotrophs → Gαq/11–PLC–IP₃/Ca²⁺cascade → GH vesicle exocytosis. It synergises with GHRH and is partly inhibited by somatostatin. Cardiovascular actions additionally involve CD36, providing GH-independent cytoprotective signalling.

2.2 Down-stream Biology

Pathway	Functional outcome	Context
GH → GHR–JAK2–STAT5	↑ IGF-1, ↑ lipolysis, ↑ protein synthesis	Liver, adipose, muscle
GHSR-AMPK/NPY-AgRP	↑ appetite, ↑ gastric motility	Hypothalamus/GI tract
CD36 → PI3K–Akt–eNOS	Anti-apoptotic, anti-fibrotic, vasodilatory	Myocardium, endothelium

3. Pharmacokinetics

Absorption/routes: SC, IV, intranasal, sublingual; oral bioavailability negligible.
Onset/peak: GH peaks ~15–30 min post-dose; returns to baseline by ~2 h.
Half-life: Short plasma t½ ~10–30 min; pharmacodynamic impact persists via IGF-1 accumulation with repeated pulses.
Clearance: Peptidase degradation; renal/hepatic peptide catabolism; no CYP interactions.

4. Pre-clinical and Translational Evidence

4.1 Endocrine & Metabolic

In healthy adults and GH-deficient cohorts, hexarelin provokes robust GH responses (often > GHRP-6) with modest IGF-1 increases over days; tachyphylaxis of GH peaks can occur with high-frequency chronic dosing.

4.2 Cardiovascular Remodelling

Across infarction, reperfusion, and pressure-overload models, hexarelin improves systolic/diastolic function, reduces apoptosis and fibrosis, and enhances coronary/endothelial function, partly independent of GH/IGF-1 via CD36–Akt–eNOS pathways.

4.3 Muscle & Bone

Models of disuse and denervation show anti-atrophy effects and faster recovery; bone studies suggest anabolic turnoverconsistent with GH-axis activation.

4.4 Sleep, Appetite, and GI

Night dosing increases SWS and appetite; GI mucosal studies demonstrate accelerated healing under inflammatory or ulcerative injury.

5. Emerging Clinical Interests

Field	Rationale	Current status
Cancer/COPD cachexia	Orexigenic + GH-anabolic synergy	Early trials/pilots
Cardio-protection (post-MI/HF)	CD36/GHSR-mediated cytoprotection	Translational/preclinical
Sarcopenic obesity	GH pulses with limited chronic IGF-1	Exploratory
Sleep SWS decline in mid-life	Augment SWS & GH	Proof-of-concept
Critical-illness catabolism	Anti-atrophy and GI mucosal protection	Preclinical/feasibility

6. Safety and Tolerability

Common: Flushing, paresthesias, transient hunger, headache, mild injection-site irritation.
Endocrine drift: Short-lived rises in prolactin and ACTH/cortisol around 30–60 min post-dose.
Glycaemia: Possible mild fasting-glucose increase; monitor in insulin resistance.
CV: Generally favourable signals preclinically; rare palpitations reported clinically.
Tachyphylaxis: GH responses may attenuate with frequent long-term dosing; intermittent schedules are often explored in research.
Contraindications/cautions: Active malignancy under anabolic-sensitive evaluation, uncontrolled diabetes, pregnancy.

Comparative safety matrix

Concern	Hexarelin	GHRP-2 (pralmorelin)	MK-677 (oral GHSR agonist)
IGF-1 elevation	Moderate, pulsatile	Moderate, pulsatile	Higher, sustained
Appetite impact	↑ (less than ghrelin/GHRP-6)	↑↑	↑
Prolactin/cortisol spike	Yes (transient)	Yes (transient)	Yes
Glucose drift	Mild ↑	Mild ↑	Moderate ↑
Routes	SC/IV/IN/SL	IV/SC/IN	Oral

7. Regulatory Landscape

Therapeutic approvals: None in major markets.
Diagnostics: Unlike GHRP-2 (approved in Japan), hexarelin is not an approved diagnostic.
Sport: Classified as a prohibited peptide hormone/secretagogue by WADA.
Access: Research-use or compounded products; quality and purity vary.

8. Future Directions

Cardio-focused development: Human studies targeting post-MI remodelling and HFpEF/HFrEF with mechanistic endpoints (strain imaging, NT-proBNP, endothelial function).
PK engineering: Lipidated or depot analogs to extend half-life and reduce dosing frequency.
Combination regimens: Pair with resistance exercise, nutrition therapy, or anti-catabolic agents in cachexia; evaluate co-therapy with GLP-1RA to temper orexigeny.
Biomarker-guided dosing: Track IGF-1 SDS, GH profiles, and CGM for glycaemic safety; explore CD36-linked biomarkers for cardiac trials.

Selected References

Ghigo E. et al. Hexarelin and GHRP pharmacology and endocrine effects. Journal of Clinical Endocrinology & Metabolism.
Bisi G. et al. Human GH responses to hexarelin vs other secretagogues. Neuroendocrinology.
Bodart V. et al. CD36-mediated cardiovascular actions of hexarelin. Circulation Research; Cardiovascular Research.
Tóth K. et al. Anti-remodelling and anti-apoptotic effects in cardiac injury. Journal of Molecular and Cellular Cardiology.
Cappello F. et al. Hexarelin and skeletal muscle preservation under unloading. Muscle & Nerve.
Nagaya N. et al. Ghrelin/secretagogues in heart failure and ischemia models. American Journal of Physiology–Heart.
Virdis A. et al. Endothelial benefits and eNOS activation with GHSR agonism. Vascular Pharmacology.
Müller A. et al. Sleep architecture changes with GHS administration. Sleep; Psychoneuroendocrinology.
World Anti-Doping Agency. Prohibited List 2025, peptide hormones and related substances.

Hexarelin 10mg vial

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