Ipamorelin – Selective GHSR Agonist & Growth Hormone Secretagogue

Chemical Identity

Chemical Name: Ipamorelin Acetate
Molecular Formula: C₃₈H₄₉N₉O₅
Molecular Weight: ~711.85 Da
CAS Number: 170851-70-4
Sequence (Linear): Aib-His-D-2-Nal-D-Phe-Lys-NH₂
Structure Type: Synthetic pentapeptide mimetic and selective ghrelin receptor agonist (GHSR-1a)

Pharmacological Classification

Ipamorelin is a highly selective growth hormone secretagogue (GHS) that functions as an agonist of the ghrelin receptor, formally known as the growth hormone secretagogue receptor type 1a (GHSR-1a). Unlike earlier GHS peptides, it is noted for its selectivity, minimal off-target activity, and lack of effects on cortisol or prolactin secretion.

Mechanism of Action

• GHSR-1a Activation: Binds GHSR-1a in the anterior pituitary and hypothalamus to stimulate pulsatile growth hormone (GH) release.
• G-protein Signaling: Activates G_q and G_i/o-coupled signaling cascades involving IP₃, DAG, and cAMP.
• Neuroendocrine Modulation: Enhances hypothalamic GHRH tone while suppressing somatostatin inhibition.

β-Arrestin Recruitment

Ipamorelin exhibits low β-arrestin recruitment at the GHSR-1a receptor compared to other secretagogues like hexarelin or ghrelin. This signaling bias reduces receptor desensitization and internalization, supporting sustained GH release during chronic exposure.

GHSR-1a Receptor Bias Profile

Ligand	GH Release	β-Arrestin Recruitment	Desensitization
Ghrelin	Strong	High	Rapid
Hexarelin	Strong	High	Marked
Ipamorelin	Moderate–Strong	Low	Minimal

Pharmacokinetics (Non-Dosing)

• Half-Life: ~2 hours (short-acting secretagogue)
• Administration Routes: Effective subcutaneously and intravenously in preclinical models
• Clearance: Hepatic and renal proteolytic degradation

Biological Effects

Promotes GH release without increasing ACTH, cortisol, or prolactin. Shown to support lean mass preservation, enhance recovery, and stimulate IGF-1 synthesis in preclinical settings. No evidence of insulin resistance, glycemic disruption, or aldosterone elevation.

Stability and Storage

• Form: Lyophilized acetate salt
• Solubility: Water, 0.01M HCl, saline, or dilute acetic acid
• Storage: –20°C; protect from light and moisture
• Reconstitution pH: 4.0–5.5 recommended

References

1. Smith RG, et al. Endocrinology. 1997;138(11):5177–5183.
2. Raun K, et al. Eur J Endocrinol. 1998;139(5):552–561.
3. Camargos ST, et al. J Pediatr Endocrinol Metab. 2010;23(11):1133–1142.
4. Moulin A, et al. Front Endocrinol. 2012;3:136.