IPAMORELIN is a small pentapeptide that binds to the receptor of ghrelin/growth hormone (GH) secretagogue, and research has suggested the peptide to be extremely selective in its mode of action.[1] Ipamorelin also does not appear to induce non-specific release of hormones like prolactin, thyroid-stimulating hormone, ACTH, luteinizing hormone, follicle-stimulating hormone, and cortisol. The high specificity of the peptide makes it an ideal model for the study of selectivity in receptor binding and also a potential candidate for therapeutic use. It appears to function through interaction with cognate receptors on the target cell surface and mediates a cellular response. Ipamorelin may induce secretions from the pituitary gland, promoting growth in animal study models.[2] In addition, it may not only trigger the expression of insulin-like growth factor-1(IGF-1) but also inhibit the secretion of somatostatin. Hence, the peptide has the potential to influence the overall growth and repair of muscles and skeletal tissues in the body.
MOLECULAR FORMULA: C38H49N9O5
MOLECULAR WEIGHT: 711.85 g/mol
SEQUENCE: Aib-His-D-2Nal-D-Phe-Lys-NH2
PUBCHEM: CID 9831659
CAS NUMBER: 170851-70-4
RECONSTITUTION: Required
IPAMORELIN AND BONE HEALTH
Prolonged use of glucocorticoids reduces bone density and can lead to fracture. Bisphosphonates, hormone therapies, and new monoclonal antibodies are used as alternative treatments though they come with their side effects and are often expensive. Reasearch in Ipamorelin therapies suggest a potential for the peptide to become an economic and physiologically safe alternative. Studies in rats have observed that the peptide may prevent bone loss from glucocorticoid treatment, and also may induce up to a four-fold increase in bone formation.[3] The researchers also reported that “the decrease in muscle strength and bone formation found in GC-injected rats was counteracted by simultaneous administration of the growth hormone secretagogue.” The peptide may improve the bone mineral density of both existing and new bones. Additionally, it may reverse side effects like muscle wasting and fat deposition in the body’s visceral organs.
IPAMORELIN AND DIABETES
Studies in murine models of diabetes have suggested a strong efficacy of Ipamorelin in promoting insulin release from islet cells of the pancreas.[4] Studies observe that the peptide may mediate the release of insulin through the indirect excitation of calcium channels found on the islet cells. The mechanism of Ipamorelin action highlights the limitations of type 2 diabetes, and further research in this area may help develop novel therapeutic medicines, and lead to more strategic and effective preventive measures.
IPAMORELIN AND NEGATIVE CORTICOSTEROID EFFECTS
Glucocorticoids are the kind of corticosteroids that are commonly administered to treat inflammation in diverse conditions ranging from cancer to autoimmune disease. Unfortunately, their adverse side effects restrict their use. Over long durations, a higher dose of these hormones is required to overcome their physiological ill effects. This treatment regimen hence can be near-fatal. Researchers studying the effects of Ipamorelin have observed the peptide’s potential to decrease the side effects of glucocorticoid use.
IPAMORELIN AND MUSCLE GROWTH
GH and GH secretagogues such as Ipamorelin may decrease the catabolic effects of glucocorticoids on muscles. Studies on Ipamorelin posit that it helps to reestablish the nitrogen balance and reduce nitrogen wasting in the liver of rats that were treated with glucocorticoids. Thus the molecule has the potential to help to overcome both muscle wasting and loss of bone density in patients who require glucocorticoids.
IPAMORELIN AS GHRELIN RECEPTOR PROBE
The peptide binds strongly to the ghrelin receptor and acts as a selective agonist. Interestingly, the ghrelin receptor has been observed to increase cardiac failure and certain types of cancer, such as human carcinomas. Researchers have proposed using Ipamorelin as a probe in positron emission tomography (PET) scans to help diagnose patients. In vitro reports have confirmed the possibility of using it.[5] The next approach would be to perform in vivo study and optimize parameters for interpretation of the results.
IPAMORELIN AND POST-OPERATIVE ILEUS
Post-operative Ileus (POI) is a common condition that often follows abdominal surgery. It is characterized by an inability of the patients to accept oral nutrition as the GI system stops functioning. It can involve pain leading to prolonged stay in hospitals and extended tenure required for recovery. Ipamorelin has been studied in multiple proof-of-concept clinical trials to determine its efficacy to reduce POI. It was found to shorten the time of uptake of the first meal by about 12 hours in POI patients.[6] The researchers concluded that “ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.” However, the trials were discarded as the company conducting them decided the efficacy of the peptide to be insufficient for a viable product. However, the use of Ipamorelin in combination with other therapies might be more useful in treating POI. Some of the research observations are as follows:
– Residual radiolabeled food remaining in the stomach of rats with POI was less after the use of Ipamorelin, even when compared to rats without POI.
– When administered Ipamorelin, the geometric location of the food was observed to be similar for both rats without POI and those with POI.
– The radiolabeled food was located more distally in the GI tract and is similar to rats without POI, after Ipamorelin is used on rats with POI.
The peptide is still not studied extensively despite its potential, including the treatment of POI. Apart from therapeutic impact, the molecule can be used to study various aspects of human physiology and disease biology in detail. A new approach of study using cutting-edge technology might shift focus back to this novel peptide.[7] The peptide has exhibited moderate side effects, low oral bioavailability, and excellent subcutaneous bioavailability in mice. The dosage (per kg) in mice does not scale to humans.
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