Ipamorelin Peptide (10MG)

Growth hormone secretagogues (GHSs) represent a class of synthetic peptides that stimulate endogenous growth hormone (GH) release by binding to receptors distinct from the GH-releasing hormone (GHRH) pathway. Early compounds such as GHR(P)-2 and GHR(P)-6 demonstrated potent GH-releasing activity in animals but lacked hormonal selectivity, often elevating ACTH and cortisol in addition to GH. The need for more selective growth hormone secretagogues peptides led researchers to explore analogs capable of stimulating GH without triggering the adrenal axis. This pursuit culminated in the discovery of ipamorelin, the first growth hormone secretagogue with exclusive GH selectivity, setting a new standard in endocrine research.

Ipamorelin is a synthetic pentapeptide with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂, developed by modifying GHR(P)-1 to eliminate the central dipeptide Ala-Trp. This structural refinement aimed to enhance receptor specificity and eliminate non-GH hormonal activity. The compound was synthesized using solid-phase peptide synthesis via both Boc and Fmoc strategies and purified to >95% by reverse-phase HPLC. Analytical NMR and mass spectrometry confirmed its molecular integrity and expected mass (±0.9 amu). As a white, water-soluble trifluoroacetate salt, ipamorelin displayed robust chemical stability and well-defined pKa values (10.3, 7.8, 6.2), enabling consistent experimental performance in vitro and in vivo assays.

In primary rat pituitary cell assays, ipamorelin demonstrated a GH release potency and efficacy comparable to GHR(P)-6 (EC₅₀ ≈ 1.3 nmol/L, Emax ≈ 85% relative activity). Antagonist profiling confirmed that GH stimulation occurred via a GHR(P)-like receptor, not through the GHRH receptor, as ipamorelin's response was inhibited by GHR(P) antagonists but unaffected by GHRH blockers. This pharmacologic pattern confirmed that ipamorelin growth hormone secretagogue acts specifically through a receptor distinct from GHRH signaling. Its ability to trigger GH release without influencing other pituitary hormones positioned it as a breakthrough in growth hormone secretagogues peptide research.

Rat Model Findings In anesthetized male rats, ipamorelin induced dose-dependent GH release with an ED₅₀ of ~80 nmol/kg and a peak GH concentration (Emax) of ~1545 ng/mL. These values were equivalent to GHR(P)-6 (ED₅₀ ≈ 115 nmol/kg, Emax ≈ 1167 ng/mL) and superior to less optimized analogs. Importantly, the replacement of the N-terminal alanine residue with Aib restored both potency and efficacy in vivo, confirming the critical role of this structural modification. Swine Model Results In conscious swine, ipamorelin again induced rapid, dose-dependent GH secretion with an ED₅₀ ≈ 2.3 nmol/kg and Emax ≈ 65 ng/mL plasma, closely matching GHR(P)-6 (ED₅₀ ≈ 3.9 nmol/kg, Emax ≈ 74 ng/mL). Although GHR(P)-2 was more potent (ED₅₀ ≈ 0.6 nmol/kg), its efficacy was lower, and it lacked hormonal selectivity. GH plasma levels returned to baseline within two hours, reflecting natural pulsatility. These results established ipamorelin as a potent and highly selective growth hormone secretagogue peptide in large-animal models.

Ipamorelin exhibited unprecedented hormonal selectivity among GH secretagogues. Even at doses exceeding 200× the GH-effective level, it produced no measurable change in ACTH, cortisol, FSH, LH, PRL, or TSH concentrations in animals. By contrast, GHR(P)-2 and GHR(P)-6 significantly increased ACTH and cortisol. Ipamorelin's lack of adrenal activation mirrored the physiological profile of endogenous GHRH, confirming that it is the first ipamorelin growth hormone secretagogue to isolate GH release from other endocrine pathways. This selective mechanism reduced potential metabolic stress associated with excess cortisol, a limitation in previous GHS analogs.

Mechanistically, ipamorelin activates a specific GHR(P) receptor—distinct from the GHRH receptor—localized in the hypothalamic-pituitary axis. This activation initiates GH release primarily through pituitary somatotrophs without stimulating the adrenal cortex. The resulting GH surge is short-lived and physiologically pulsatile, aligning closely with endogenous secretion rhythms. These pharmacodynamic properties suggest that ipamorelin can elevate GH levels while preserving homeostatic balance, offering insights into designing growth hormone secretagogues peptides that minimize systemic side effects.

Ipamorelin's receptor selectivity and safety profile make it a model growth hormone secretagogue peptide for research. Its targeted GH stimulation supports exploration in muscle wasting, sarcopenia, frailty, and GH deficiency syndromes, where anabolic recovery is beneficial without cortisol elevation. Compared to earlier secretagogues, ipamorelin offers reduced adrenal stimulation, lower risk of metabolic disruption, and enhanced mimicry of physiologic GH pulsatility. These characteristics also render it valuable for regenerative and metabolic studies where GH modulation must remain precise and transient.

The animals study established ipamorelin as the first selective GHR(P) receptor agonist capable of stimulating GH release with no concurrent activation of ACTH or cortisol pathways. This discovery marked a pivotal advance in growth hormone secretagogue development, proving that selective GH stimulation is achievable. Ipamorelin's unique receptor specificity, consistent in vitro and in vivo efficacy, and absence of adrenal activation position it as a foundational model for next-generation GHR(P) analogs designed for safer clinical translation and refined endocrine research.