A 5-amino-acid synthetic peptide that selectively stimulates growth hormone release through the ghrelin/GHS receptor. Considered the 'cleanest' GH secretagogue because it does not significantly affect cortisol, prolactin, or aldosterone levels.
Ipamorelin is a synthetic pentapeptide growth hormone secretagogue (GHS) that acts on the ghrelin receptor (GHS-R1a) in the pituitary gland. It was developed by Novo Nordisk in the late 1990s and is notable for being the most selective GH secretagogue discovered — it stimulates GH release without significantly affecting cortisol, prolactin, ACTH, or aldosterone levels.
Ipamorelin is commonly combined with CJC-1295 in clinical peptide protocols. The rationale is complementary receptor targeting: CJC-1295 stimulates GH release through the GHRH receptor, while ipamorelin stimulates it through the ghrelin receptor. Together, they produce greater GH pulses than either peptide alone.
Ipamorelin binds to the GHS-R1a, a Gq-coupled GPCR primarily expressed on pituitary somatotrophs. Activation triggers PLC-mediated calcium release from intracellular stores, which promotes fusion of GH-containing secretory granules with the cell membrane. This pathway is independent of and synergistic with the GHRH-Gs-cAMP pathway (targeted by CJC-1295), which is why combining the two peptides produces amplified GH release.
| Pathway | Effect | Significance |
|---|---|---|
| Selective GH release | Activates GHS-R1a on somatotrophs without HPA axis activation | GH increase without cortisol, prolactin, or aldosterone changes |
| Preserved pulsatility | Amplifies natural GH pulses rather than creating flat elevation | More physiological GH profile than exogenous GH injection |
| Synergy with CJC-1295 | Ghrelin receptor + GHRH receptor dual stimulation | Greater GH amplitude than either peptide alone |
| Minimal hunger effect | Less ghrelin-like appetite stimulation than GHRP-6 | Better tolerated and fewer food cravings |
| IGF-1 increase | GH-mediated hepatic IGF-1 production | Downstream anabolic and repair effects |
| Study | Design | Findings | Level |
|---|---|---|---|
| GH release | Phase I/II, healthy volunteers | Dose-dependent GH increase; peak at 30-60 min post-injection; no significant cortisol or prolactin changes | Level II |
| Selectivity comparison | Preclinical + clinical | Ipamorelin is more selective than GHRP-6 (which increases cortisol and hunger) and GHRP-2 (which increases cortisol and prolactin) | Level II |
| Post-surgical recovery | Phase II, abdominal surgery | Improved GI recovery and reduced hospital stay in post-surgical patients | Level II |
| CJC-1295 combination | Clinical research | Synergistic GH release documented; commonly used protocol in anti-aging medicine | Level II-III |
Generally well-tolerated: No significant adverse effects at standard research doses.
Transient side effects: Mild headache, flushing, dizziness reported in some subjects — typically resolve quickly.
Water retention: GH elevation can cause fluid retention and joint stiffness.
Long-term unknown: No long-term safety data. Same theoretical cancer risk as any GH-elevating therapy.
| Jurisdiction | Status |
|---|---|
| FDA | Not approved. Novo Nordisk discontinued clinical development. |
| WADA | Banned under S2 (Peptide hormones and growth factors) |
| Availability | Available as a research chemical |