Ipamorelin

Product description

What is Ipamorelin?

Ipamorelin (NNC 26-0161) is a synthetic pentapeptide (a peptide made up of five amino acids) with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂. It was developed by the Danish company Novo Nordisk in the late 1990s as a derivative of growth hormone-releasing peptide (GHRP-1).

Ipamorelin belongs to the class of growth hormone secretagogues (GHS – Growth Hormone Secretagogues), substances that stimulate the secretion of endogenous growth hormone by the pituitary gland. It is classified as an agonist of the growth hormone secretagogue receptor (GHS-R1a), also known as the ghrelin receptor – an endogenous hormone produced mainly in the stomach.

A unique feature of ipamorelin, distinguishing it from other peptides in this class (such as GHRP-2 or GHRP-6), is its high selectivity for growth hormone release without a significant effect on the secretion of other pituitary hormones.

Mechanism of action

Ipamorelin works by precisely activating the GHS-R1a receptor, which leads to a cascade of molecular events:

Activation of the ghrelin receptor (GHS-R1a) – Ipamorelin mimics the action of ghrelin by binding to its receptor in the pituitary gland. This increases cyclic AMP (cAMP) production in somatotroph cells, which stimulates the synthesis and release of growth hormone (GH).

Hormonal selectivity – In studies on pigs, ipamorelin significantly increased plasma GH levels without significant changes in ACTH, cortisol, prolactin, FSH, LH, or TSH concentrations. This selectivity distinguishes it from GHRP-2 and GHRP-6, which also raise cortisol and ACTH levels.

Pulsatile GH release – Ipamorelin induces a physiological, pulsatile pattern of growth hormone release, mimicking natural circadian rhythms. Peak GH concentrations occur about 40 minutes after administration, after which levels quickly return to baseline.

IGF-1 cascade – Elevated GH levels stimulate the liver to produce insulin-like growth factor 1 (IGF-1), which mediates many of the anabolic effects of growth hormone on peripheral tissues.

Scientific research directions

Ipamorelin is the subject of preclinical and early clinical research in several therapeutic areas:

Studies on body composition and metabolism

Growth hormone plays a key role in regulating fat and protein metabolism. Studies in animal models are examining the effect of ipamorelin on lipolysis (fat breakdown), muscle protein synthesis, and overall body composition. In a 9-week study in GH-deficient mice, ipamorelin induced weight gain, with no organomegaly (enlargement of internal organs) observed, distinguishing it from exogenous growth hormone.

Studies on bone mineral density

Growth hormone and IGF-1 are important regulators of bone metabolism. In a 12-week study in adult female rats, ipamorelin increased bone mineral content (BMC) measured by DXA. The increase in cortical bone cross-section suggests stimulation of bone formation from the periosteal side. In another study in rats receiving glucocorticosteroids, ipamorelin increased periosteal bone formation rate fourfold, counteracting the catabolic effects of steroids.

Studies on long bone growth

In studies in rats, ipamorelin administered subcutaneously for 15 days increased the longitudinal growth rate of long bones in a dose-dependent manner. This effect suggests potential applications in the context of growth disorders in children, although this requires confirmation in clinical studies.

Gastroenterological studies

The GHS-R1a receptor is found not only in the pituitary but also in the gastrointestinal tract. Preclinical studies in models of postoperative ileus (POI – postoperative ileus) showed that ipamorelin accelerated gastric emptying and restored gastrointestinal motility. In a randomized phase II clinical trial in patients after bowel resection, ipamorelin was well tolerated, although the primary endpoints did not reach statistical significance.

Studies on steroid-induced catabolism

Glucocorticosteroids cause protein catabolism and muscle weakness. In animal models, ipamorelin reduced increased hepatic urea synthesis, improved nitrogen balance, and normalized nitrogen content in organs in prednisolone-treated rats, suggesting potential for counteracting the side effects of chronic steroid therapy.

Studies on aging

Aging is associated with a decline in endogenous GH and ghrelin secretion. GHS-R1a receptor agonists are being studied for their ability to restore a youthful hormonal profile. Studies in old mice using similar agonists have shown partial restoration of thymus function and improvement in muscle mass and bone density.

Scientific context

Ipamorelin is part of the broader field of growth hormone secretagogue research, which includes both peptides (GHRP-2, GHRP-6, hexarelin) and non-peptide compounds (ibutamoren/MK-677, macimorelin). Among this class of compounds, ipamorelin stands out for:

• The highest selectivity for GH release among peptide GHS
• The absence of a significant effect on the hypothalamic-pituitary-adrenal (HPA) axis
• A safety profile comparable to GHRH (growth hormone-releasing hormone)

Macimorelin, a non-peptide GHS-R1a agonist, has received FDA approval as a diagnostic test for adult growth hormone deficiency, confirming the clinical potential of this class of compounds.

Safety profile in studies

In published preclinical and early clinical studies, ipamorelin has shown a favorable safety profile:

• In a phase II study in patients after bowel resection, ipamorelin at a dose of 0.03 mg/kg twice daily for 7 days was well tolerated
• The most common adverse effects included transient injection-site reactions
• No significant changes in ACTH and cortisol levels were observed even at doses 200 times higher than the ED50 for GH release

The long-term safety profile requires further clinical research.

Bibliography – latest scientific studies

1. Sinha DK, Balasubramanian A, Tatem AJ, et al. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020;9(Suppl 2):S149-S159. PMC
2. Ishida J, Saitoh M, Ebner N, et al. Growth hormone secretagogues: history, mechanism of action, and clinical development. JCSM Rapid Commun. 2020;3(1):25-37. Wiley
3. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014;29(12):1527-34. PubMed
4. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-61. PubMed
5. Andersen NB, Malmlöf K, Johansen PB, et al. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res. 2001;11(5):266-72. PubMed
6. Johansen PB, Nowak J, Skjærbæk C, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999;9(2):106-13. PubMed
7. Aagaard NK, Grøfte T, Greisen J, et al. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth Horm IGF Res. 2009;19(3):252-8. PubMed
8. Svensson J, Lall S, Dickson SL, et al. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000;165(3):569-77. PubMed
9. Smith RG, Sun Y, Ber E, et al. Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging. Ann N Y Acad Sci. 2007;1119:147-64. PubMed
10. Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012;4:149-55. PMC