Description of Ipamorelin

In terms of efficacy, ipamorelin has similar or higher potency compared to GHRP-6 in various animal models, but it stands out due to its unique lack of effect on other hormones such as prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), PRL, and thyroid stimulating hormone (TSH). This makes ipamorelin a promising candidate for further clinical development as it provides targeted GH release without the additional stress response typically associated with other GH secretagogues. Ipamorelin was originally developed by company Novo Nordisk, and was investigated in phase II clinical trials by Helsinn Therapeutics for treatment of postoperative ileus.

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Research Confirmed Effects

1. Ipamorelin and Negative Corticosteroid Effects

Ipamorelin has shown promising effects in counteracting the catabolic impacts of glucocorticoids (GC) on muscle strength and bone formation in adult rats. In a study involving 8-month-old female rats injected with methylprednisolone (GC), the combination treatment with Ipamorelin significantly increased muscle strength and periosteal bone formation. Specifically, the maximum tetanic tension of the calf muscles was higher, and the bone formation rate was four times greater in rats treated with both GC and Ipamorelin compared to those injected with GC alone. This finding suggests that Ipamorelin can mitigate the negative effects of glucocorticoids on muscle and bone, providing a therapeutic avenue to maintain skeletal muscle function and bone formation during GC treatment.

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2. Ipamorelin and Bone Mineral Density

In a related study, Ipamorelin and GHRP-6 were evaluated for their effects on bone mineral content (BMC) in young adult female rats. The research indicated that both GHS compounds increased body weight and total tibial and vertebral BMC measured by dual X-ray absorptiometry (DXA). However, total BMC, when adjusted for body weight, remained unchanged. The increased bone formation was attributed to larger bone dimensions and increased cortical cross-sectional area, as determined by in vitro measurements with peripheral quantitative computed tomography (pQCT) and Archimedes' principle. Although cortical volumetric bone mineral density (BMD) and mineral concentration remained unchanged, the findings suggest that GHS treatments can lead to an increase in bone size without necessarily impacting bone density. These studies point to the potential benefits of Ipamorelin and other GHS compounds in supporting bone health and countering muscle and bone degradation.

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3. Ipamorelin and Muscle Growth

Given that glucocorticoids often lead to muscle wasting, the potential of GH and its secretagogues to reduce catabolic effects is crucial. The ability of ipamorelin to decrease nitrogen wasting and improve organ nitrogen content in rats treated with prednisolone suggests that it may serve as effective treatments to prevent muscle atrophy and other catabolic effects in patients requiring steroid therapy. By counteracting muscle loss and maintaining nitrogen balance, these substances could provide significant clinical benefits, helping to manage the adverse side effects of glucocorticoid treatment and enhancing patient outcomes.

Growth hormone (GH) and growth hormone secretagogues like ipamorelin have been shown to mitigate the catabolic effects of glucocorticoids on nitrogen balance and urea synthesis in the liver. In a study involving rats, prednisolone, a glucocorticoid, was found to increase the hepatic capacity for urea-N synthesis (CUNS) and elevate the expression of urea cycle genes, which contributes to nitrogen loss. This treatment also led to a decrease in nitrogen balance and reduced nitrogen content in various organs. However, co-administration of GH reduced CUNS by 33%, normalized urea cycle gene expression, and improved nitrogen balance by 2.5 times. Similarly, ipamorelin decreased CUNS by 20%, reduced the expression of urea cycle enzymes, and improved nitrogen balance, albeit less efficiently than GH.

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4. Ipamorelin and Diabetes

Ipamorelin has shown to stimulate insulin release from the pancreas of both normal and diabetic rats. In a study investigating the mechanism of this effect, researchers used pancreatic tissue fragments from normal and diabetic rats. The results indicated that ipamorelin evoked significant increases in insulin secretion at varying concentrations. This insulin-stimulating effect could be inhibited by different agents such as diltiazem, yohimbine, propranolol, or a combination of atropine, propranolol, and yohimbine. Interestingly, atropine caused a significant reduction in ipamorelin-induced insulin secretion in diabetic but not in normal rats.

The implications of these results are particularly relevant for understanding the treatment of diabetes. The ability of ipamorelin to potentiate insulin release suggests that this compound could play a role in developing new therapies for diabetes mellitus, particularly type 2 diabetes, where insulin secretion is impaired. Further research on ipamorelin's interaction with the calcium channels and adrenergic receptors in the pancreas could lead to novel therapeutic approaches to enhance insulin secretion and manage glucose levels in diabetic patients. This study lays the groundwork for exploring ipamorelin's potential in this field.

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5. Ipamorelin and Postoperative Ileus

Postoperative ileus (POI) is a significant complication following certain types of surgery, especially after bowel resection. It is characterized by delayed gastrointestinal motility, leading to increased hospital stay and longer recovery times. This condition is marked by abdominal discomfort, bloating, and an inability to tolerate oral nutrition. Recent studies have explored the potential of ipamorelin, a ghrelin receptor agonist, in accelerating gastrointestinal recovery in patients with POI.

Proof-of-concept clinical trials have assessed the safety and efficacy of ipamorelin in reducing POI symptoms. In a randomized controlled study, intravenous administration of ipamorelin was evaluated in patients undergoing abdominal surgery. Results suggested that ipamorelin reduced the time to first tolerated meal by approximately 7 hours, compared to placebo. However, the results were not statistically significant, indicating limited efficacy, and need of more specific research.

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6. Ipamorelin as a Ghrelin Receptor Probe

The ghrelin receptor is overexpressed in various conditions like human carcinoma and heart failure, making it a potential target for disease diagnosis and staging. Researchers have been exploring the use of positron emission tomography (PET) imaging to detect ghrelin receptor activity. Recent work has focused on the development of PET probes from peptidic and peptidomimetic derivatives of growth hormone secretagogues (GHSs). This opens up new possibilities for tracking ghrelin receptor activity in different diseases, and ipamorelin is able to bind ghrelin receptors very strongly.

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References

1. K. Raun et al., “Ipamorelin, the first selective growth hormone secretagogue,” Eur. J. Endocrinol., vol. 139, no. 5, pp. 552–561, Nov. 1998. [PubMed]
2. N. B. Andersen, K. Malmlöf, P. B. Johansen, T. T. Andreassen, G. Ørtoft, and H. Oxlund, “The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats,” Growth Horm. IGF Res. Off. J. Growth Horm. Res. Soc. Int. IGF Res. Soc., vol. 11, no. 5, pp. 266–272, Oct. 2001. [PubMed]
3. J. Svensson et al., “The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats,” J. Endocrinol., vol. 165, no. 3, pp. 569–577, Jun. 2000. [PubMed]
4. N. K. Aagaard et al., “Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats,” Growth Horm. IGF Res. Off. J. Growth Horm. Res. Soc. Int. IGF Res. Soc., vol. 19, no. 5, pp. 426–431, Oct. 2009. [PubMed]
5. E. Adeghate and A. S. Ponery, “Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats,” Neuro Endocrinol. Lett., vol. 25, no. 6, pp. 403–406, Dec. 2004. [PubMed]
6. D. E. Beck, W. B. Sweeney, M. D. McCarter, and 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., vol. 29, no. 12, pp. 1527–1534, Dec. 2014. [PubMed]