â–ŽIpa Research
What is the research background of Ipa?
Delayed gastric emptying is a common condition, and currently, there are few effective treatment options. Research has found that Ipa, as a synthetic peptidomimetic, acts on the ghrelin receptor and may have a therapeutic effect on delayed gastric emptying. In a study on a rodent model of gastroparesis, gastroparesis was induced by abdominal surgery and intestinal manipulation, and it was found that Ipa could accelerate gastric emptying[1].
Postoperative ileus is a significant challenge in clinical practice, lacking effective management strategies. Ghrelin receptor stimulation has a motility-promoting effect on both the upper and lower parts of the gastrointestinal tract. As a ghrelin receptor agonist, Ipa has potential application value in the treatment of postoperative ileus. For example, in a study, a prospective, randomized, controlled proof-of-concept study was conducted on patients undergoing intestinal resection after abdominal surgery to evaluate the safety and effectiveness of Ipa[2].
Ipa belongs to the growth hormone releasing peptides (GHRPs), which is a synthetic pentapeptide capable of stimulating the release of growth hormone from the hypothalamus and pituitary gland. Growth hormone plays an important role in the body’s growth, repair, and metabolism, so the role of Ipa in regulating growth hormone has also attracted widespread attention[3].
Due to its potential value in treating delayed gastric emptying, postoperative ileus, and its role as a growth hormone releasing peptide, Ipa has attracted extensive research attention.
What is the mechanism of action of Ipa?
1. Stimulating the release of growth hormone:Â
Ipa belongs to the growth hormone releasing peptides (GHRPs), which can stimulate the release of growth hormone from the hypothalamus and pituitary gland. In vitro and in vivo experiments, Ipa has shown high potency and efficacy in releasing growth hormone. For example, in a study, the potency and efficacy of Ipa in releasing growth hormone from primary rat pituitary cells were similar to those of GHRP-6[3]. Its mechanism of action is to stimulate the release of growth hormone by activating GHRP-like receptors. Through pharmacological analysis, it has been confirmed that like GHRP-6, Ipa stimulates the release of growth hormone through GHRP-like receptors.
2. Effects on the gastrointestinal tract
Accelerating gastric emptying:Â
In rodent models, Ipa can accelerate gastric emptying. Abdominal surgery leads to delayed gastric emptying, but after administration of Ipa (0.014 µmol/kg intravenously), gastric emptying is significantly accelerated. Ipa stimulates gastric contractility and accelerates gastric emptying through a mechanism mediated by the activation of the ghrelin receptor, involving cholinergic excitatory neurons (Greenwood-Van Meerveld B, 2012).
Improving symptoms of postoperative ileus:Â
In rodent models of postoperative ileus, Ipa may improve the symptoms. After postoperative administration of Ipa, a single dose of Ipa (1mg/kg) or GHRP-6 (20μg/kg) can reduce the time to first defecation. Repeated administration of Ipa (0.1 or 1mg/kg) can significantly increase the cumulative fecal output, food intake, and weight gain [4].
3. Effects on insulin secretion
Ipa can stimulate insulin secretion in pancreatic tissue fragments of normal and diabetic rats. The increase in insulin secretion induced by Ipa can be significantly inhibited by diltiazem, yohimbine, propranolol, or a combination of atropine, propranolol, and yohimbine. In diabetic rats, atropine can significantly reduce the insulin secretion induced by Ipa, but this effect is not observed in normal rats. This indicates that Ipa stimulates insulin release through the calcium channel and adrenergic receptor pathways[5].
4. Alleviating pain
In experimental models of non-inflammatory visceral hypersensitivity and somatic mechanical allodynia, Ipa, as a peripherally restricted ghrelin receptor agonist, can significantly reduce colonic hypersensitivity and somatic allodynia. Its mechanism of action is mediated by the ghrelin receptor, and this antinociceptive effect can be blocked by the ghrelin receptor antagonist H0900[6].
Shows the effect of ipamorelin on insulin secretion from pancreatic tissue fragments of normal and diabetic rats.
Source:PubMed[5]
What are the applications of Ipa?
1. Promoting the release of growth hormone
Ipa can stimulate the release of growth hormone from the hypothalamus and pituitary gland. Growth hormone plays an important role in the human body, including promoting protein synthesis, cell proliferation, and tissue repair. Therefore, Ipa can be used to treat growth hormone deficiency or other diseases related to growth hormone insufficiency[7].
2. Improving gastrointestinal function
Accelerating gastric emptying:Â
In rodent models, Ipa accelerates gastric emptying in models of postoperative ileus through a mechanism mediated by the activation of the growth hormone releasing peptide receptor, involving cholinergic excitatory neurons[1]. Abdominal surgery leads to delayed gastric emptying, and administration of Ipa can significantly reduce the proportion of residual food in the stomach, thereby improving gastric motility.
 Promoting gastrointestinal peristalsis:Â
In rodent models of postoperative ileus, Ipa may improve the symptoms of patients. For example, in a rat model, Ipa can reduce the time to first defecation after surgery, increase fecal output, food intake, and weight gain[4]. Repeated administration of Ipa can significantly increase the cumulative fecal output, food intake, and weight gain, indicating its positive regulatory effect on gastrointestinal function.
3. Relieving pain
Relieving visceral and somatic pain:Â
Research shows that Ipa, as a growth hormone releasing peptide receptor agonist, has antinociceptive properties. In experimental models without colonic epithelial inflammation, Ipa can significantly reduce non-inflammatory visceral hypersensitivity and somatic mechanical allodynia[6].
Its mechanism of action may be mediated by the growth hormone releasing peptide receptor, participating in the regulation of visceral and somatic hypersensitivity, providing a potential new method for the treatment of acute visceral and somatic pain.
What are the research progress of Ipa in the treatment of growth hormone deficiency?
Growth hormone deficiency is a disease caused by insufficient secretion of growth hormone from the anterior pituitary gland, which can affect the growth and development of children and the body metabolism of adults. In recent years, Ipa, as a growth hormone secretagogue, has attracted widespread attention in the treatment of growth hormone deficiency. The following is the relevant research progress of Ipa in the treatment of growth hormone deficiency.
1. The stimulating effect of Ipa on growth hormone secretion
Ipa can stimulate the secretion of growth hormone. Research shows that Ipa can act synergistically with growth hormone releasing hormone (GHRH) to enhance the release of growth hormone[8]. In animal experiments, after 21 days of chronic treatment with Ipa in young female rats, compared with the control group, the basal growth hormone release in the monolayer culture of pituitary cells increased. At the same time, Ipa and GHRH can stimulate the release of growth hormone from cultured pituitary cells in vitro. However, in the GHRH pretreatment group, the subsequent growth hormone response to stimulation was not enhanced, while in the Ipa pretreatment group, there was no such desensitization phenomenon, indicating that Ipa does not lead to desensitization of the growth hormone response in young female rats[8].
2. The effect of Ipa on weight gain
Chronic administration of Ipa can effectively increase the weight of young female rats. Daily monitoring shows that the percentage of weight gain in the Ipa pretreatment group and the GHRH pretreatment group is higher than that in the control group[8]. This is related to the fact that Ipa stimulates the secretion of growth hormone, which in turn promotes protein synthesis and cell growth.
3. The effect of Ipa on bone formation
In an adult rat model, it has been found that the growth hormone secretagogue Ipa can counteract the catabolic effects of glucocorticoids (GC) on skeletal muscle and bone. Compared with the group injected with GC alone, in the animals injected with both GC and Ipa, the maximum tetanic tension of the calf muscle increased significantly, and the periosteal bone formation rate increased fourfold [8, 9]. This indicates that Ipa has a positive effect on maintaining muscle strength and promoting bone formation, and may help prevent complications such as osteoporosis in patients with growth hormone deficiency.
4. The effect of Ipa on gastrointestinal function
As a selective growth hormone-releasing hormone agonist and growth hormone-releasing peptide receptor agonist, Ipa demonstrated therapeutic efficacy in a mouse model of postoperative intestinal paralysis. Single administration of Ipa or growth hormone-releasing peptide (GHRP)-6 shortened the time to the first postoperative bowel movement, but had no effect on cumulative fecal output, food intake, or weight gain. Ipa increases cumulative fecal output, food intake, and weight gain. This suggests that Ipa may have a certain role in improving gastrointestinal function and may help improve digestive and absorptive function in patients with growth hormone deficiency.[4].
In summary, as a selective growth hormone secretion promoter, Ipa efficiently stimulates the release of growth hormone by activating the growth hormone-releasing peptide receptor (GHS receptor), without significantly affecting the levels of adrenocorticotropic hormone (ACTH) and cortisol. Its functions include promoting growth hormone secretion, regulating gastrointestinal motility, and alleviating pain. Its high selectivity and multi-target characteristics confer clinical application potential, making it suitable for use in conditions such as growth hormone deficiency, postoperative intestinal obstruction, and pain management.
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