Ipamorelin

Ipamorelin is the first synthetic GHS that appears highly selective and may have the potential to increase hGH production without affecting other pituitary hormones such as prolactin or adrenocorticotropic hormone (ACTH). The potential increase in hGH could promote lipolysis and the synthesis of insulin-like growth factor-1 (IGF-1) production. Consequently, IGF-1 may become a mediator of the anabolic actions of hGH, and thus the peptide may act to increase cell proliferation and bone and muscle anabolism.(1)

Chemical Composition

• Molecular Formula: C38H49N9O5
• Molecular Weight: 711.86 g/mol
• Other Known Titles: NNC 26-0161

Based on a 1998 murine model-based research study, researchers suggested that Ipamorelin may release growth hormones from pituitary cells. When Ipamorelin was presented to pentobarbitone-anesthetized pigs and rats, it reportedly exhibited growth hormone releasing activity. Upon further observation, researchers hypothesized that, similarly to other growth hormone (GH) stimulating peptides, Ipamorelin may be a growth receptor agonist stimulating GH release through potential affinity at growth hormone receptors. Furthermore, researchers commented that Ipamorelin appears to be the first GHS-R “agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of Ipamorelin makes this compound a very interesting candidate for future clinical development.”(1) Scientific research studies have also suggested that Ipamorelin may lead to increased hGH secretion, possibly without significantly affecting other pituitary hormones such as prolactin or ACTH levels.(2)

In vitro studies suggest that the interaction of Ipamorelin with GHS receptors may potentially affect somatotroph cells in the anterior pituitary gland by triggering a series of cellular signaling events.(3) This theorized pathway involves the activation of phospholipase C (PLC), which some researchers believe may lead to increased release of inositol triphosphate (IP3) and diacylglycerol (DAG). This release of secondary messenger molecules like IP3 could potentially stimulate the discharge of calcium ions (Ca2+) from the cell's internal stores, while DAG could activate protein kinase C (PKC). The subsequent increase in intracellular calcium levels and potential activation of PKC are believed to result in the exocytosis of growth hormone-filled vesicles from these pituitary cells.(3)

In late 1999, a clinical trial was conducted in eight test subjects where Ipamorelin was presented every 15 minutes over a set period. Two hours post-study, researchers suggested that growth hormone levels had apparently increased. More specifically, Ipamorelin appeared to have tended to increase growth hormone levels, potentially rising up to 80mIU/l (approximately equivalent to a concentration of about 26.6ng/ml). When this increase is measured as a percentage compared to a placebo (with a baseline of 1.31mIU/l or 0.4ng/ml), the improvement appeared to have exceeded a 60-fold increase.(4)

It is conceivable that Ipamorelin may positively influence bone mineral density. The theory postulates that Ipamorelin could stimulate osteoblasts (cells responsible for bone formation) through hGH-mediated mechanisms, potentially leading to their enhanced proliferation, growth, and specialization. In a particular study, murine models were exposed to Ipamorelin or a placebo.(5) The impact of Ipamorelin on bone mineral density in these mice was closely monitored via real-time dual-energy X-ray absorptiometry (DEXA) assessments at critical sites, including the femur and L6 vertebra. Following the experiment, femur bones were further examined using peripheral quantitative computed tomography of the mid-diaphysis (pQCT). Preliminary findings implied that the peptide may have contributed to increased body mass and a likely elevation in overall tibial and vertebral BMC (bone mineral content) detected by DEXA compared to the placebo group. Furthermore, pQCT data appeared to suggest that the observed increase in cortical BMC may have stemmed from an enlargement in the bone's cross-sectional area. Conversely, cortical volumetric bone mineral density (BMD, denoting the ratio of BMC to area) appeared to remain stable. Therefore, there may have been an enlargement in femur and L6 vertebrae volumes as BMC appeared to increase while volumetric BMDs appeared unchanged.(5)

Researchers have delved into Ipamorelin's potential in stomach functionality, with keen interest in its ability to possibly accelerate the gastric emptying process. For instance, one study employed a technique to determine gastric emptying rates, which involved monitoring the proportion of a labeled substance remaining in the stomach 15 minutes after its introduction via intragastric gavage.(6) Scientists performed surgeries to purposely decelerate the gastric emptying process in murine models. This deceleration was particularly notable in the control group. Conversely, Ipamorelin appeared to have markedly accelerated the emptying process compared to the control. This observation led the team to hypothesize that Ipamorelin might be capable of increasing gastric emptying speed. Further investigation was initiated to delve into the compound's action on the contractile potential of stomach smooth muscles, which were activated by acetylcholine and electric field stimulation. Indeed, decelerated peristalsis appeared to differ when Ipamorelin and ghrelin were studied together, suggesting the notion that Ipamorelin may enhance gastric smooth muscle contractility.(6)

Ipamorelin's potential actions on ghrelin receptors may lead to an enhancement in hunger signals and, perhaps, a consequent increase in body mass. Research suggests that research models exposed to Ipamorelin were observed to maintain an estimated 15% increase in body weight.(7) Researchers speculate this substance might have led to a proportional increase in fat pad weight compared to total body weight. Consequently, DEXA scans might indicate a comparative increase in body fat percentage. Furthermore, there is speculation among researchers that Ipamorelin might elevate serum leptin levels, a hormone considered to play a crucial role in energy balance and hunger regulation. This observation has led scientists to consider increased food consumption as a potential contributor to the weight gain observed in research models exposed to Ipamorelin. They have postulated that "GHSs increase body fat by GH-independent mechanisms that may include increased feeding.”(7)

Researchers have suggested that Ipamorelin may potentially mediate anabolic action, which may be due to its potential in hGH and IGF-1 synthesis and can be assessed through its impact on nitrogen balance. In a distinct investigation, researchers aimed to explore Ipamorelin's action on specific liver markers associated with alpha-amino-nitrogen conversion during induced catabolic states.(8) The study focused on the liver's capacity to synthesize urea-N (CUNS), which can serve as an indicator of the organ's ability to process nitrogen. Messenger RNA (mRNA) levels related to hepatic urea cycle enzymes were analyzed, alongside an assessment of overall nitrogen balance and a hypothesis on nitrogen distribution in various organs. Findings suggested that Ipamorelin might have contributed to a possible 20% reduction in CUNS compared to the artificially induced catabolic condition. Furthermore, it might have decreased the expression of urea cycle enzymes, possibly restored nitrogen balance, and theoretically altered or improved nitrogen concentrations in different organs.(8)