Abstract
Ipamorelin is a selective synthetic pentapeptide belonging to the growth hormone secretagogue (GHS) family. It functions as a ghrelin receptor (GHS-R1a) agonist, stimulating pulsatile release of growth hormone (GH) with minimal impact on other pituitary hormones such as prolactin, ACTH, or cortisol. Compared to earlier GHS molecules (e.g., GHRP-6, Hexarelin), Ipamorelin demonstrates improved receptor selectivity and safety. This review summarizes its mechanism of action, applications in research, experimental dosing, and limitations.
1. Introduction
Growth hormone secretagogues (GHS) are compounds that activate the ghrelin receptor to stimulate GH release. Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) was developed as a highly selective GHS with reduced off-target endocrine effects. Its ability to mimic the natural pulsatile secretion of GH has made it of interest for research in endocrinology, metabolism, and regenerative biology.
2. Mechanism of Action
- Receptor: Ipamorelin binds to GHS-R1a (the ghrelin receptor).
- Action: Stimulates GH release from pituitary somatotrophs.
- Selectivity: Minimal activity on ACTH, cortisol, or prolactin compared to earlier peptides.
- Secondary effects: GH surge leads to increased hepatic IGF-1 production, mediating anabolic and metabolic effects.
3. Research Findings
3.1 Endocrinology & GH axis
- Demonstrated consistent GH release in animal and human studies.
- Short-acting but mimics natural pulsatility, which may be advantageous compared to exogenous GH administration.
3.2 Metabolic & body composition
- Preclinical work suggests potential reductions in fat mass and improvements in lean body mass through IGF-1–mediated pathways.
- Explored in the context of sarcopenia, cachexia, and metabolic disorders.
3.3 Tissue repair & regeneration
- GH/IGF-1 pathway stimulation is associated with accelerated recovery and repair in musculoskeletal and connective tissues.
- Investigated in wound healing and post-injury recovery models.
3.4 Aging research
- Potential use in age-related GH decline has been considered, though long-term human studies are limited.
4. Typical Experimental Dosing
⚠️ Note: These are research-only ranges from preclinical and limited human studies, not medical recommendations.
- Animal studies: 10–100 μg/kg per dose, typically via injection.
- Human studies (phase I/II trials):
- Single-dose studies: ~0.005–0.03 mg/kg IV bolus increased GH secretion within minutes.
- Fixed dosing in peptide research: 100–300 μg subcutaneous injections, administered 1–3 times daily, are commonly reported.
- Combination research: Frequently studied alongside GHRH analogues (e.g., CJC-1295) for synergistic GH release.
5. Safety & Limitations
- Adverse effects (reported): mild injection site irritation, transient flushing, headache.
- Endocrine profile: lower risk of prolactin or cortisol elevation compared to GHRP-6 or Hexarelin.
- Long-term safety: Not established; human trials are limited and short in duration.
- Regulatory status: Not FDA-approved; considered experimental.
6. Conclusion
Ipamorelin is a highly selective growth hormone secretagogue with favorable pharmacologic properties compared to earlier peptides. It produces physiologic, pulsatile GH release with minimal off-target hormonal activity. Research suggests applications in endocrinology, metabolism, regenerative biology, and aging. However, clinical translation remains limited, and long-term safety data are lacking.
7. References (sample)
- Raun K, et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol.
- Svensson J, et al. (2000). Endocrine effects of ipamorelin in humans. Growth Horm IGF Res.
- Bowers CY. (2001). Uncoupling of growth hormone secretion from ACTH, cortisol, and prolactin by ipamorelin. J Clin Endocrinol Metab.
⚠️ Disclaimer: Ipamorelin is an experimental peptide. All dosing information reflects research studies only and does not imply safe or approved human use.
