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

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

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

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

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.