Ipamorelin

What is Ipamorelin?

Ipamorelin is a growth hormone releasing peptide (GHRP) and one of the most selective growth hormone secretagogues available. Unlike other GHRPs, ipamorelin stimulates growth hormone (GH) release with minimal impact on other hormones like cortisol and prolactin, making it a preferred choice for researchers studying GH-related pathways.

Developed in the mid-1990s, ipamorelin represents a significant advancement in peptide selectivity. Its ability to promote growth hormone release without the side effects associated with less selective compounds has made it one of the most extensively studied peptides in regenerative medicine research.

Research Note: Ipamorelin is a research compound not approved by the FDA for human use. It is banned in competitive sports by WADA. This information is for educational purposes only.

Discovery and Development

Origins

Ipamorelin was developed by Novo Nordisk in 1998 through systematic modifications of earlier growth hormone releasing peptides. The goal was to create a highly selective GH secretagogue with minimal side effects.

Key Milestones

• 1998: Initial development and characterization by Novo Nordisk
• 1999-2001: Early preclinical studies establish selectivity profile
• 2005-2010: Extensive research into mechanism and applications
• 2010s: Becomes widely used in research settings
• Present: Ongoing studies in various therapeutic applications

Molecular Profile

Chemical Structure

Ipamorelin is a pentapeptide (five amino acids) with the sequence:

Aib-His-D-2-Nal-D-Phe-Lys-NH2

Where:

• Aib = 2-aminoisobutyric acid
• D-2-Nal = D-2-naphthylalanine
• The C-terminus is amidated (-NH2)

Key Molecular Data

Structural Significance

The unique amino acid modifications in ipamorelin contribute to its selectivity:

• Aib residue: Increases stability and receptor selectivity
• D-amino acids: Protect against enzymatic degradation
• Amidated C-terminus: Improves binding and stability

Mechanism of Action

Primary Mechanism: GHS-R Activation

Ipamorelin works primarily through the growth hormone secretagogue receptor (GHS-R), also known as the ghrelin receptor:

Step-by-step mechanism:

1. Binds to GHS-R in the pituitary gland
2. Activates G-protein coupled signaling cascades
3. Increases intracellular calcium release
4. Stimulates growth hormone secretion from somatotroph cells
5. GH enters circulation and activates downstream pathways

Selectivity Profile

What makes ipamorelin unique is its highly selective action:

Growth Hormone Cascade

Once GH is released, it triggers a cascade of effects:

1. Direct effects: GH acts directly on tissues
2. IGF-1 production: Liver produces insulin-like growth factor 1
3. Local IGF-1: Tissues produce IGF-1 locally
4. Metabolic effects: Fat metabolism, protein synthesis
5. Growth effects: Cell proliferation and tissue repair

Research Applications

Body Composition Studies

Research has explored ipamorelin's effects on body composition:

Key Findings:

• Increased lean body mass in animal models
• Reduced adipose tissue accumulation
• Improved body composition ratios
• Enhanced protein synthesis markers

Bone Health Research

Significant research has focused on skeletal effects:

Observed Effects:

• Increased bone mineral density in studies
• Enhanced osteoblast activity markers
• Improved bone healing rates in fracture models
• Potential applications in osteoporosis research

Sleep and Recovery

The pulsatile nature of ipamorelin-induced GH release:

• Mimics natural nocturnal GH patterns
• Associated with improved sleep quality in research
• Enhanced recovery markers in animal studies
• Potential synergy with natural sleep-related GH release

Gastrointestinal Research

The GHS-R's presence in the GI tract has led to studies on:

• Gastric motility effects
• Potential gastroprotective properties
• GI healing and recovery
• Appetite and satiety regulation

Cardiovascular Research

Emerging research examines cardiac effects:

• Cardioprotective potential
• Effects on cardiac output
• Vascular function studies
• Post-ischemic recovery research

Comparison with Other GHRPs

Ipamorelin vs GHRP-6

Ipamorelin vs GHRP-2

Ipamorelin vs Hexarelin

Synergistic Combinations

Ipamorelin + CJC-1295

The most studied combination in research:

Rationale:

• CJC-1295 (GHRH analog) stimulates GH synthesis
• Ipamorelin (GHRP) amplifies GH release
• Together, they produce synergistic GH elevation

Research Findings:

• Combined effect greater than either alone
• More sustained GH elevation
• Maintained pulsatile release pattern
• Widely studied protocol in research

Ipamorelin + GHRH Analogs

Other GHRH analogs can be combined:

• Sermorelin
• Modified GRF (1-29)
• Tesamorelin

Research Administration

Common Research Protocols

In published studies, ipamorelin is typically administered:

Routes:

• Subcutaneous injection (most common)
• Intravenous (clinical studies)
• Intraperitoneal (animal studies)

Timing Considerations:

• Often administered in fasted state
• Multiple daily doses studied
• Evening administration explored (sleep studies)

Stability and Storage

Lyophilized (Powder):

• Store at -20°C for long-term
• Stable at 2-8°C for weeks
• Protect from light and moisture

Reconstituted:

• Use bacteriostatic water
• Store at 2-8°C
• Use within 4-6 weeks
• Avoid freeze-thaw cycles

Safety Profile in Research

Observed Side Effects

Based on published research:

Common:

• Injection site reactions (minor)
• Transient headache
• Flushing (rare)

Uncommon:

• Lightheadedness
• Fatigue
• Water retention

Selectivity Advantage

The minimal cortisol and prolactin stimulation means:

• Reduced stress hormone effects
• No prolactin-related issues observed
• Better overall tolerability in studies
• More consistent results

Contraindication Considerations

Research excludes subjects with:

• Active malignancy
• Pituitary disorders
• Pregnancy or nursing
• Hypersensitivity to peptides

Regulatory Status

FDA Status

• Not approved for human therapeutic use
• Available for research purposes
• Investigational compound

WADA Status

• Prohibited substance (S2 category)
• Banned in-competition and out-of-competition
• Detectable via testing

Research Availability

• Available from research chemical suppliers
• Requires appropriate research credentials in some jurisdictions
• Quality varies by supplier

Frequently Asked Questions

How does ipamorelin differ from synthetic HGH?

Ipamorelin stimulates the body's natural GH production through the pituitary gland, maintaining pulsatile release patterns. Synthetic HGH provides exogenous hormone directly. Ipamorelin preserves feedback mechanisms while HGH may suppress natural production.

Does ipamorelin cause hunger like GHRP-6?

No. One of ipamorelin's advantages is minimal effect on appetite. GHRP-6 strongly stimulates ghrelin-related hunger, while ipamorelin's selective receptor binding avoids this effect.

How long does ipamorelin's effect last?

The acute GH pulse from ipamorelin lasts approximately 3 hours. However, the downstream effects of elevated GH and IGF-1 persist longer, contributing to cumulative research effects.

Can ipamorelin be taken orally?

No. Like most peptides, ipamorelin would be degraded by digestive enzymes. Injection is the required route for systemic effects. Some research explores alternative delivery systems.

Is ipamorelin safe?

Research studies show a favorable safety profile with minimal side effects due to its selectivity. However, long-term human safety data is limited, and it remains an investigational compound.

Key Research References

1. Raun, K., et al. (1998). "Ipamorelin, the first selective growth hormone secretagogue." European Journal of Endocrinology, 139(5), 552-561.

2. Johansen, P.B., et al. (1999). "Pharmacokinetic and pharmacodynamic profile of ipamorelin in rats." European Journal of Pharmacology, 367(2-3), 255-261.

3. Beck, D.E., et al. (2004). "Effect of ipamorelin on muscle wasting in rats." Journal of Surgical Research, 122(2), 219-225.

4. Svensson, J., et al. (2000). "Two months of treatment with the growth hormone secretagogue ipamorelin." Clinical Endocrinology, 53(5), 665-673.

5. Hansen, B.S., et al. (1999). "The effect of the growth hormone secretagogues ipamorelin and GH-releasing peptide-6 on growth and body composition in rats." Growth Hormone & IGF Research, 9(3), 222-229.

Summary

Ipamorelin stands out among growth hormone releasing peptides for its exceptional selectivity and favorable safety profile. Its ability to stimulate robust GH release without affecting cortisol, prolactin, or appetite makes it uniquely suited for research applications.

Key Points:

• Classification: Selective growth hormone releasing peptide (GHRP)
• Mechanism: GHS-R activation with high selectivity
• Primary advantage: Minimal side effects compared to other GHRPs
• Research focus: Body composition, bone health, recovery
• Common pairing: Often studied with CJC-1295 or GHRH analogs
• Status: Research compound, not FDA-approved

The combination of efficacy and selectivity has made ipamorelin one of the most extensively studied peptides in growth hormone research. Its clean pharmacological profile continues to drive interest in potential therapeutic applications.