Description

Ipamorelin

For Research & Laboratory Use Only

Overview

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue (GHS), with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂. It was specifically developed to act through the ghrelin receptor, also known as the growth hormone secretagogue receptor (GHS-R). These receptors are expressed in several tissues, including the pituitary gland, which naturally governs human growth hormone (hGH) production.

By binding to GHS-R on pituitary somatotroph cells, Ipamorelin is hypothesized to promote pulsatile GH release in experimental models, making it a subject of interest in growth hormone physiology research.(1)

Mechanistic Profile

Ipamorelin is often described in the literature as one of the first highly selective GHS compounds, with a strong preference for stimulating GH release while minimally affecting other pituitary hormones such as prolactin or adrenocorticotropic hormone (ACTH).(1,2)

Through its potential to increase circulating GH, Ipamorelin may:

• Support lipolytic pathways

• Promote synthesis of insulin-like growth factor-1 (IGF-1)

• Indirectly influence anabolic processes such as cellular proliferation and bone and muscle tissue development via IGF-1–mediated signaling(1)

Chemical Makeup

• Molecular Formula: C₃₈H₄₉N₉O₅

• Molecular Weight: 711.86 g/mol

• Other Known Titles: NNC 26-0161

Research and Experimental Studies

1. Ipamorelin and Selective GHS-R Agonism

A foundational 1998 study in animal models evaluated Ipamorelin’s impact on GH release.(1) When presented to swine and pentobarbitone-anesthetized rats, Ipamorelin appeared to:

• Stimulate GH secretion from pituitary cells

• Act as a GHS-R agonist with a selectivity profile similar to GHRH for GH release

Importantly, researchers noted that Ipamorelin’s action seemed largely restricted to GH, with minimal impact on prolactin and ACTH secretion.(1,2) This selectivity made it stand out among early-generation GHS compounds and positioned it as a candidate of interest for continued investigation.

2. Ipamorelin and Growth Hormone Secretion Pathways

In vitro studies examining pituitary somatotrophs suggest that Ipamorelin’s interaction with GHS-R may trigger a cascade of intracellular signaling events.(3) Proposed mechanisms include:

• Activation of phospholipase C (PLC)

• Increased production of second messengers inositol triphosphate (IP₃) and diacylglycerol (DAG)

• IP₃-mediated release of Ca²⁺ from intracellular stores

• DAG-mediated activation of protein kinase C (PKC)

The combined rise in intracellular calcium and PKC activation is thought to promote exocytosis of GH-containing vesicles from anterior pituitary cells.

A small human study in 1999, involving repeated Ipamorelin administration every 15 minutes, reported marked increases in circulating GH.(4) Peak concentrations reportedly reached ~80 mIU/L (~26.6 ng/mL), compared with a baseline near 1.31 mIU/L (~0.4 ng/mL), representing an approximate 60-fold increase versus placebo.

3. Ipamorelin and Bone Tissue

Research in adult female rat models has explored Ipamorelin’s influence on bone mineral content (BMC) and bone structure.(5) In these experiments:

• Animals received either Ipamorelin or placebo

• Bone parameters were monitored using dual X-ray absorptiometry (DEXA) at key sites such as the femur and L6 vertebra

• Additional assessment was done with peripheral quantitative CT (pQCT) of the femoral mid-diaphysis

Findings suggested:

• Increased body mass in Ipamorelin-exposed animals

• Apparent increases in overall tibial and vertebral BMC vs. placebo

• pQCT data indicated that higher cortical BMC was primarily associated with larger cross-sectional bone area, rather than increased volumetric bone mineral density (BMD)

In other words, bones appeared to become larger in volume (greater area and BMC) while volumetric BMD remained stable, implying geometric changes rather than density changes per se.(5)

4. Ipamorelin and Gastric Motility

Investigators have also examined Ipamorelin’s potential actions on gastric function, particularly gastric emptying rates.(6) In rodent models:

• Gastric emptying was quantified by measuring the percentage of a labeled solution remaining in the stomach 15 minutes after intragastric administration

• Surgical procedures were used to induce delayed gastric emptying in control animals

In contrast to delayed controls, Ipamorelin-exposed animals showed:

• Faster gastric emptying

• Mitigation of slowed peristalsis

Additional experiments evaluating gastric smooth muscle contractility indicated that Ipamorelin, especially when assessed alongside ghrelin, might enhance smooth muscle contractile responses elicited by acetylcholine and electrical field stimulation.(6) These observations suggest a potential prokinetic effect in experimental models.

5. Ipamorelin, Appetite, and Body Composition

Due to its action on ghrelin receptors, Ipamorelin may also influence feeding behavior and energy balance. In one animal study, growth hormone secretagogues such as Ipamorelin were associated with:

• ~15% increase in body weight in research models

• Relative increases in fat pad mass vs. total body weight

• A higher body fat percentage as measured by DEXA(7)

Researchers proposed that these changes may be due, at least in part, to:

• Increased food intake

• Possible elevations in serum leptin, a hormone involved in satiety and energy regulation

The authors concluded that GHS compounds may increase adiposity through GH-independent mechanisms, which may include enhanced feeding behavior.(7)

6. Ipamorelin and Nitrogen Balance

Ipamorelin has also been evaluated in the context of nitrogen balance and urea synthesis during catabolic conditions.(8) In steroid-treated rat models:

• Investigators monitored hepatic capacity for urea-N synthesis (CUNS) as a marker of nitrogen disposal

• mRNA expression of urea cycle enzymes was measured

• Overall nitrogen balance and distribution across organs was assessed

Findings suggested that Ipamorelin exposure:

• May reduce CUNS by ~20% versus catabolic controls

• Might diminish expression of urea cycle enzymes

• Appeared to improve nitrogen balance and potentially alter nitrogen partitioning among organs(8)

These findings support the concept that Ipamorelin may contribute to anabolic or nitrogen-sparing effects under specific experimental conditions, possibly through GH and IGF-1–related mechanisms.

Research-Use Only Disclaimer

Ipamorelin from OptiBuild Peptides is supplied exclusively for laboratory, scientific, and in-vitro research purposes.
It is not intended for human or veterinary use, medical treatment, or diagnostic procedures.
All purchasers are required to comply with our Terms and Conditions and all applicable regulations.

References

1. Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Endocrinology. 1998.

2. Sinha DK, et al. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020;9(Suppl 2):S149-S159.

3. Jiménez-Reina L, et al. Influence of chronic treatment with Ipamorelin in young female rats: somatotroph response in vitro. Histol Histopathol. 2002;17(3):707–714.

4. Gobburu JVS, Agersø H, Jusko WJ, et al. Pharmacokinetic-pharmacodynamic modeling of Ipamorelin in human volunteers. Pharm Res. 1999;16:1412–1416.

5. Svensson J, et al. The GH secretagogues ipamorelin and GHRP-6 increase bone mineral content in adult female rats. J Endocrinol. 2000;165(3):569–577.

6. Greenwood-Van Meerveld B, et al. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012;4:149–155.

7. Lall S, et al. Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochem Biophys Res Commun. 2001;280(1):132–138.

8. Aagaard NK, 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(5):426–431.