Ipamorelin
⚠️ Structural Separation Notice
The Ageless Pep Academy is a clinical education property independent from any commerce operation. Any references in this profile to Ageless Peps product SKUs, pricing, or the agelesspeps.com domain are for completeness and transparency; they are not endorsements and do not form part of the clinical education content. Clinicians are responsible for independent verification of any product sourcing decision. The Academy's Medical Director provides editorial oversight only and does not endorse commercial products.
Selective growth hormone secretagogue and GHS-R1a (ghrelin receptor) agonist; the first GHRP shown to stimulate GH release without affecting cortisol, prolactin, or ACTH levels.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | NNC 26-0161, Ipamorelin acetate |
| Category | GH Axis / Muscle Growth / Anti-Aging / Sleep |
| Sequence | Aib-His-D-2-Nal-D-Phe-Lys-NH2 (pentapeptide, 5 amino acids) |
| Molecular Weight | ~711.9 Da |
| Molecular Formula | C38H49N9O5 |
| PubChem CID | 9831659 |
| Administration | SubQ / IV |
| Typical Dose Range | 100-300 mcg per injection (from literature) |
| Half-Life | ~2 hours |
| Storage | Lyophilized: -20C for 1-2 years; Reconstituted: 2-8C, use within 2-4 weeks |
| FDA Status | Research only. Phase II clinical trial completed for postoperative ileus (did not advance to Phase III). |
| WADA Status | Prohibited (S2 – Peptide Hormones, Growth Factors, Related Substances) |
Mechanism of Action
Ipamorelin is a pentapeptide growth hormone releasing peptide (GHRP) that acts as a selective agonist of the growth hormone secretagogue receptor 1a (GHSR/GHS-R1a, UniProt Q92847), also known as the ghrelin receptor. It was identified as "the first selective growth hormone secretagogue" because, unlike earlier GHRPs (GHRP-2, GHRP-6, Hexarelin), ipamorelin stimulates robust GH (GH1, UniProt P01241) release from pituitary somatotrophs without elevating cortisol, prolactin, or ACTH at therapeutic doses (PMID 9849822).
This selectivity arises from ipamorelin's unique receptor binding profile. While it activates GHS-R1a to trigger GH release, it does not engage the off-target receptor interactions responsible for the neuroendocrine side effects seen with non-selective GHRPs. GHRP-6, for example, stimulates appetite via ghrelin mimicry and elevates cortisol; hexarelin causes prolactin elevation at higher doses. Ipamorelin produces a clean GH pulse without these confounders, making it the best-tolerated GHRP in its class.
The GH secretory mechanism is complementary to — and independent from — the GHRH pathway. GHRH acts via GHRH receptors to initiate GH synthesis, while GHS-R1a agonists amplify the release signal and partially suppress somatostatin (the GH inhibitory hormone). When ipamorelin is co-administered with a GHRH analog such as CJC-1295 NO DAC, the dual receptor activation produces a supra-additive GH pulse approximately 7-10x greater than either agent alone. This synergistic combination has become the benchmark protocol for physiological GH optimization.
Beyond GH secretion, ipamorelin has demonstrated prokinetic activity in postoperative ileus models. The ghrelin receptor is expressed in the GI tract, and ipamorelin stimulates gastric motility through this pathway, leading to Phase II clinical investigation for postoperative ileus management (PMID 25331030).
Key Research Areas
- Selective GH secretion – First GHRP demonstrated to release GH without cortisol/prolactin/ACTH elevation
- Postoperative ileus – Phase II RCT for GI motility recovery post-surgery via ghrelin receptor agonism
- Bone metabolism – Counteracts glucocorticoid-induced bone loss in animal models
- Longitudinal bone growth – Stimulates linear growth in juvenile rats, relevant to growth disorders
- Pharmacokinetics – Well-characterized PK/PD profile including nasal absorption studies
- Cachexia / chemotherapy support – Inhibits cisplatin-induced weight loss in ferret models
- Body composition – GH-mediated lean mass accretion and fat oxidation
- Synergistic GH protocols – Combined GHRH + GHRP studies for amplified GH release
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 2 | Phase II postoperative ileus; PK/PD in volunteers |
| Human observational | 0 | — |
| Animal in vivo | 5 | Bone growth, bone loss, GI motility, cisplatin cachexia, GH dose-response |
| In vitro | 1 | Nasal absorption PK |
| Systematic reviews | 0 | — |
| Narrative reviews | 3 | GHS body composition, sports medicine, musculoskeletal review |
Clinical Applications
- Fat Loss — GH-mediated lipolysis without cortisol-driven fat deposition
- Sarcopenia — GH-IGF-1 driven lean mass accretion and protein synthesis
- Injury Recovery — IGF-1 tissue repair signaling
- Sleep Disorders — Amplification of natural slow-wave sleep GH pulse when dosed at bedtime
Protocols Using This Peptide
Ageless Peps Products
- AP-Ipamorelin-Vial — Ipamorelin Vial, $40 (WC 691)
- AP-CJC-Ipam-Blend — CJC-1295 NO DAC / Ipamorelin Blend, $64 (WC 780)
- AP-Tesa-Ipam-Blend — Tesamorelin / Ipamorelin Blend, $119 (WC 785)
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ | 100 mcg (with CJC-1295 ND) | 1-3x daily, fasted | 8-12 weeks on / 4 weeks off | PMID 9849822; practitioner consensus |
| SubQ | 100-200 mcg (standalone) | 2-3x daily, fasted | 8-12 weeks | Less effective than combination |
| SubQ | 100-200 mcg (sleep optimization) | Once at bedtime | Ongoing | Amplifies slow-wave sleep GH pulse |
| IV | 1 mcg/kg (clinical trial) | Post-surgery | Acute | PMID 25331030 (postop ileus trial) |
Cycling
Standard cycling: 5 days on / 2 days off; 8-12 weeks on / 4 weeks off. MUST be administered in a fasted state (minimum 2 hours post-meal). Pre-sleep dosing is optimal for maximizing the natural slow-wave sleep GH pulse. Dose-response studies indicate 100 mcg produces substantial GH release; 200-300 mcg offers marginal additional benefit with increased side effect risk.
Contraindications & Safety
- Contraindications: Active malignancy (IGF-1 elevation theoretical concern); acromegaly (absolute contraindication); active pituitary tumors
- Common side effects: Mild transient fluid retention, head rush at injection, injection site reactions. Best-tolerated GHRP in class.
- Drug interactions: Insulin and oral hypoglycemics (monitor glucose); glucocorticoids (GH effects may be blunted); somatostatin analogs (will block GH release)
- Pregnancy/nursing: Contraindicated; no safety data
- Special populations: Favorable safety profile vs. other GHRPs; no cortisol/prolactin concerns; caution in diabetics
Synergistic Combinations
- CJC-1295 NO DAC + Ipamorelin — Primary benchmark combination; 7-10x supra-additive GH pulse via dual GHRH-R + GHS-R1a activation
- Tesamorelin + Ipamorelin — Alternative GHRH pairing; FDA-approved GHRH analog for visceral fat targeting
- BPC-157 + Ipamorelin — Recovery + GH-mediated tissue repair
- AOD-9604 + Ipamorelin — Body composition stack: targeted lipolysis + GH pulse
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-9849822 – Ipamorelin, the first selective growth hormone secretagogue. | Ipamorelin, the first selective growth hormone secretagogue | 1998 | Animal in vivo |
| PMID-9879640 – Pharmacokinetic evaluation of ipamorelin and other peptidyl | Pharmacokinetic evaluation of ipamorelin and peptidyl GHS | 1998 | PK study |
| PMID-10373343 – Ipamorelin, a new growth-hormone-releasing peptide, induces | Ipamorelin induces longitudinal bone growth in rats | 1999 | Animal in vivo |
| PMID-10496658 – Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a gr | PK-PD modeling of ipamorelin in human volunteers | 1999 | Human PK/PD |
| PMID-11735244 – Ipamorelin Counteracts Glucocorticoid Bone Loss | Ipamorelin counteracts glucocorticoid-induced bone loss | 2001 | Animal in vivo |
| PMID-19289567 – Ipamorelin in Rodent Postoperative Ileus Model | Ipamorelin in rodent postoperative ileus model | 2009 | Animal in vivo |
| PMID-25331030 – Ipamorelin for Postoperative Ileus Phase II RCT | Ipamorelin for postoperative ileus: Phase II RCT | 2014 | Human RCT |
| PMID-39043357 – The growth hormone secretagogue receptor 1a agonists, anamor | GHS-R1a agonists inhibit cisplatin-induced weight loss in ferrets | 2024 | Animal in vivo |
| PMID-32257855 – Growth Hormone Secretagogues in Body Composition Management | Growth hormone secretagogues in body composition management | 2020 | Review |
| PMID-41476424 – Injectable Peptide Therapy Primer for Sports Medicine | Injectable peptide therapy primer for sports medicine | 2024 | Review |
| PMID-41966639 – Peptide Therapies for Musculoskeletal and Athletic Performance | Peptide therapies for musculoskeletal and athletic performance | 2024 | Review |
Shared Research with CJC-1295 NO DAC
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-15817669 – CJC-1295 Discovery and Identification | CJC-1295 discovery (synergy context) | 2005 | Preclinical |
| PMID-17018654 – CJC-1295 Pulsatile GH Secretion in Humans | CJC-1295 pulsatile GH secretion (combination context) | 2006 | Human PK/PD |
| PMID-16352683 – Prolonged stimulation of growth hormone (GH) and insulin-lik | Prolonged GH/IGF-1 stimulation (combination context) | 2006 | Human RCT |
References
- PMID 9849822 — First selective GHS identification
- PMID 25331030 — Phase II RCT for postoperative ileus
- PMID 10496658 — Human PK/PD modeling
- PMID 11735244 — Glucocorticoid bone loss counteraction
- PMID 39043357 — Cisplatin cachexia prevention
Related
#peptide #gh-axis #subq #iv