Ipamorelin

Product description

What is Ipamorelin?

Ipamorelin (NNC 26-0161) is a synthetic pentapeptide (a peptide composed 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 secretogens (GHS), substances that stimulate the secretion of endogenous growth hormone by the pituitary gland. It is classified as an agonist of the growth hormone secretogen receptor (GHS-R1a), also known as the ghrelin receptor - an endogenous hormone produced mainly in the stomach.

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

Mechanism of action

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

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

Hormonal selectivity – In studies in 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 increase cortisol and ACTH levels.

Pulsatile GH release – Ipamorelin induces a physiological, pulsatile pattern of growth hormone release, mimicking natural circadian rhythms. The peak of GH concentration occurs approximately 40 minutes after administration, after which the level quickly returns to baseline values.

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.

Directions of scientific research

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

Body composition and metabolism research

Growth hormone plays a key role in regulating fat and protein metabolism. Studies in animal models analyze the effect of ipamorelin on lipolysis (fat tissue breakdown), muscle protein synthesis and overall body composition. In a 9-week study in GH-deficient mice, ipamorelin induced weight gain without organomegaly (enlargement of internal organs), which distinguishes it from exogenous growth hormone.

Bone mineral density research

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) as measured by DXA. An increase in the cross-section of cortical bone suggests stimulation of bone formation from the periosteum. In another study in rats receiving glucocorticoids, ipamorelin quadrupled the rate of periosteal bone formation, counteracting the catabolic effects of steroids.

Research on the growth of long bones

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

Gastroenterological tests

The GHS-R1a receptor is present not only in the pituitary gland, but also in the gastrointestinal tract. Preclinical studies in models of postoperative intestinal obstruction (POI) 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.

Research on steroid catabolism

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

Aging research

Aging is associated with a decline in endogenous GH and ghrelin secretion. GHS-R1a receptor agonists are being investigated for restoring a youthful hormonal profile. Studies in old mice using similar agonists showed partial restoration of thymus function and improvement in muscle mass and bone density.

Scientific context

Ipamorelin fits into the broader field of research on growth hormone secretogens, which includes both peptides (GHRP-2, GHRP-6, hexarelin) and non-peptide compounds (ibutamoren/MK-677, makimorelin). Among this class of compounds, ipamorelin stands out:

• Highest selectivity for GH release among peptide GHS
• No significant effect on the hypothalamic-pituitary-adrenal (HPA) axis
• Safety profile comparable to GHRH (growth hormone releasing hormone)

Maquimorelin, a non-peptide GHS-R1a agonist, has received FDA approval as a diagnostic test for growth hormone deficiency in adults, supporting the clinical potential of this class of compounds.

Research safety profile

Ipamorelin has demonstrated a favorable safety profile in published preclinical and early clinical studies:

• In a phase II study in patients after intestinal resection, ipamorelin at a dose of 0.03 mg/kg twice daily for 7 days was well tolerated
• The most common side 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 studies.

Bibliography - latest scientific research

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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 Res1999;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 interventional 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