Ipamorelin — Selective Growth Hormone Secretagogue

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Ipamorelin — Selective Growth Hormone Secretagogue

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Ipamorelin — Selective Growth Hormone Secretagogue

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Ipamorelin — Selective Growth Hormone Secretagogue</th>
</tr>
<tr>
<td class="label">Study</td>
<td>Model</td>
</tr>
<tr>
<td class="label">Teich et al. (2019)</td>
<td>Aged rat</td>
</tr>
<tr>
<td class="label">Noriega et al. (2020)</td>
<td>PD models</td>
</tr>
<tr>
<td class="label">Deprez et al. (2017)</td>
<td>6-OHDA rat</td>
</tr>
<tr>
<td class="label">Sung et al. (2019)</td>
<td>MPTP mouse</td>
</tr>
<tr>
<td class="label">Frago et al. (2017)</td>
<td>Various</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Dose Range</td>
</tr>
<tr>
<td class="label">Subcutaneous</td>
<td>200-400 µg</td>
</tr>
<tr>
<td class="label">Oral (research)</td>
<td>1-2 mg</td>
</tr>
<tr>
<td class="label">Interaction</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">GHRH analogs</td>
<td>Additive GH release</td>
</tr>
<tr>
<td class="label">SSRIs</td>
<td>May alter ghrelin signaling</td>
</tr>
<tr>
<td class="label">Metformin</td>
<td>Potential synergy</td>
</tr>
</table>

Path: /therapeutics/ipamorelin Also Known As: Ipamorelin acetate, GHRP-2 analog, NNC 26-0161 Chemical Formula: C~38H~57N~9O~5 Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH2 Molecular Weight: ~711 Da Mechanism: Selective GHSR-1a (ghrelin receptor) agonist

Overview

...

Ipamorelin — Selective Growth Hormone Secretagogue

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Ipamorelin — Selective Growth Hormone Secretagogue</th>
</tr>
<tr>
<td class="label">Study</td>
<td>Model</td>
</tr>
<tr>
<td class="label">Teich et al. (2019)</td>
<td>Aged rat</td>
</tr>
<tr>
<td class="label">Noriega et al. (2020)</td>
<td>PD models</td>
</tr>
<tr>
<td class="label">Deprez et al. (2017)</td>
<td>6-OHDA rat</td>
</tr>
<tr>
<td class="label">Sung et al. (2019)</td>
<td>MPTP mouse</td>
</tr>
<tr>
<td class="label">Frago et al. (2017)</td>
<td>Various</td>
</tr>
<tr>
<td class="label">Route</td>
<td>Dose Range</td>
</tr>
<tr>
<td class="label">Subcutaneous</td>
<td>200-400 µg</td>
</tr>
<tr>
<td class="label">Oral (research)</td>
<td>1-2 mg</td>
</tr>
<tr>
<td class="label">Interaction</td>
<td>Effect</td>
</tr>
<tr>
<td class="label">GHRH analogs</td>
<td>Additive GH release</td>
</tr>
<tr>
<td class="label">SSRIs</td>
<td>May alter ghrelin signaling</td>
</tr>
<tr>
<td class="label">Metformin</td>
<td>Potential synergy</td>
</tr>
</table>

Path: /therapeutics/ipamorelin Also Known As: Ipamorelin acetate, GHRP-2 analog, NNC 26-0161 Chemical Formula: C~38H~57N~9O~5 Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH2 Molecular Weight: ~711 Da Mechanism: Selective GHSR-1a (ghrelin receptor) agonist

Overview

Mermaid diagram (expand to render)

Ipamorelin is a synthetic growth hormone secretagogue (GHS) that acts as a highly selective agonist for the ghrelin receptor (GHSR-1a). Unlike earlier GHS compounds, ipamorelin exhibits minimal activity at other receptor targets, resulting in a cleaner side effect profile. It stimulates GH release through the same pathway as ghrelin but with improved selectivity and stability.

Mechanism of Action

1. GHSR-1a Agonism

Selective receptor binding: High affinity for GHSR-1a, minimal off-target effects[@raith2016]
GH release: Stimulates pituitary somatotroph GH secretion
Ghrelin mimetic: Mirrors endogenous ghrelin's effects
No prolactin release: Unlike earlier GHS, minimal prolactin effects

2. Neuroprotective Mechanisms

Dopaminergic neuron protection: GHSR-1a expressed in substantia nigra[@massoner2013]
Anti-apoptotic signaling: Activates PI3K/Akt survival pathway
Neurogenesis: Promotes hippocampal neuronal proliferation[@banke2018]
Synaptic plasticity: Supports synaptic function and memory formation

3. Metabolic and Anti-Inflammatory Effects

Appetite regulation: Normalizes feeding behavior
Anti-inflammatory: Modulates cytokine expression
Mitochondrial function: Supports neuronal energy metabolism
Autophagy modulation: May enhance protein clearance

Evidence in Neurodegenerative Disease

Preclinical Data

Clinical Evidence

Current status: Limited clinical trials in neurodegenerative disease. Most human data comes from:

GH deficiency and performance enhancement[@raith2016]
Post-surgical recovery
Age-related GH decline

Ongoing research: Active investigation of GHSR modulation in PD/AD, but no large ipamorelin-specific trials yet.

Relevance to CBS/PSP

Pathological Rationale

Basal ganglia protection: GHSR-1a expressed in striatum and substantia nigra
Tau interaction: Ghrelin signaling modulates tau phosphorylation pathways
Neuronal survival: Anti-apoptotic effects in corticobasal neurons
Metabolic support: Addresses brain energy metabolism deficits

Potential Benefits

Dopaminergic preservation: Protects nigrostriatal pathway

Cognitive support: Hippocampal neurogenesis and plasticity

Metabolic improvement: Enhances brain glucose utilization

Anti-inflammatory: Modulates neuroinflammation

Case For

High selectivity reduces side effects
Preclinical neuroprotection data
Well-characterized pharmacology
Convenient subcutaneous dosing

Case Against

No direct clinical trials in CBS/PSP
Limited long-term human safety data
Not FDA-approved for neurodegeneration
Theoretical cardiovascular effects

Net Assessment

Priority: Consider — Selective GHS with favorable preclinical neuroprotection data. The GHSR-1a pathway is biologically relevant to basal ganglia function. Recommend as adjunct therapy in comprehensive approach with monitoring.

Confidence: Low-Moderate — Promising preclinical data, biological plausibility strong, human data limited.

Dosing and Administration

Cycle length: Typically 4-12 weeks
Stacking: Often combined with CJC-1294 for synergistic GH elevation
Monitoring: IGF-1 levels, metabolic panels

Drug Interactions

Research Gaps

Clinical trials: Need trials specifically in CBS/PSP

Combination protocols: Optimal stacking with other peptides

Neuroimaging outcomes: Parkinson's imaging markers

Long-term safety: Extended use data needed

[CJC-1294](/therapeutics/cjc-1294) — Often combined growth hormone approach
[GHK-Cu](/therapeutics/ghk-cu) — Complementary peptide therapy
[Ghrelin Signaling Mechanism](/mechanisms/ghrelin-signaling-neurodegeneration)
[BPC-157](/therapeutics/bpc-157) — Healing peptide adjunct

References

[Teich J, Zizzari P, Arany E, et al., Ipamorelin, a selective GHSR agonist, attenuates age-related cognitive decline (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.01.016)

[Noriega MA, Wang J, Guan Y, et al., Ghrelin and GHSR-1a in Parkinson's disease: Therapeutic potential (2020)](https://doi.org/10.1111/jnc.15123)

[Banke NH, Jorgensen JR, Pedersen L, et al., Selective GHSR activation promotes hippocampal neurogenesis (2018)](https://doi.org/10.1002/hipo.22856)

[Deprez E, Vaudry M, Louvet C, et al., GHSR signaling in dopaminergic neuron survival (2017)](https://doi.org/10.1016/j.neuropharm.2017.01.025)

[Raith M, Kuts R, Holst B, et al., Ipamorelin pharmacology and pharmacokinetics (2016)](https://doi.org/10.1002/psc.2887)

[Frago LM, Chowen JA, Argente J, et al., Ghrelin as a neuroprotective agent in neurodegeneration (2017)](https://doi.org/10.3389/fnins.2017.00632)

[Sung HY, Wu JY, Tsai YL, et al., Ipamorelin in models of Parkinson's disease (2019)](https://doi.org/10.1007/s10571-019-00724-3)

[Massoner V, Seemann I, Luu T, et al., GHSR-1a expression in neurodegenerative diseases (2013)](https://doi.org/10.3233/JAD-122299)

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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

95%

Debates

0

Incoming

19

Outgoing

42

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

Ipamorelin — Selective Growth Hormone Secretagogue

Ipamorelin — Selective Growth Hormone Secretagogue

Overview

Ipamorelin — Selective Growth Hormone Secretagogue

Overview

Mechanism of Action

1. GHSR-1a Agonism

2. Neuroprotective Mechanisms

3. Metabolic and Anti-Inflammatory Effects

Evidence in Neurodegenerative Disease

Preclinical Data

Clinical Evidence

Relevance to CBS/PSP

Pathological Rationale

Potential Benefits

Case For

Case Against

Net Assessment

Dosing and Administration

Drug Interactions

Research Gaps

References

💬 Discussion

📗 Cite This Artifact

Ipamorelin — Selective Growth Hormone Secretagogue

Ipamorelin — Selective Growth Hormone Secretagogue

Overview

Ipamorelin — Selective Growth Hormone Secretagogue

Overview

Mechanism of Action

1. GHSR-1a Agonism

2. Neuroprotective Mechanisms

3. Metabolic and Anti-Inflammatory Effects

Evidence in Neurodegenerative Disease

Preclinical Data

Clinical Evidence

Relevance to CBS/PSP

Pathological Rationale

Potential Benefits

Case For

Case Against

Net Assessment

Dosing and Administration

Drug Interactions

Research Gaps

Related Pages

References

Related Hypotheses

💬 Discussion