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Research Monograph

Ipamorelin (Growth Hormone Secretagogue)

Also Known AsNNC 26-0161 · Ipamorelin Acetate

Molecular Weight711.85 g/mol
Discovered1998
Citations4 peer-reviewed
Research Areas4 domains
Background

Developed by Novo Nordisk as a highly selective growth hormone secretagogue peptide (GHSP). Identified through systematic modification of GHRP peptides to eliminate unwanted cortisol and prolactin release while retaining potent GH-releasing activity. First described in the late 1990s.

Amino Acid SequenceAib-His-D-2-Nal-D-Phe-Lys-NH2
Mechanisms of Action

How Ipamorelin Works

01

GHS-R1a (Ghrelin Receptor) Agonism

Selectively activates the growth hormone secretagogue receptor type 1a (GHS-R1a), a G-protein-coupled receptor expressed on pituitary somatotrophs. Unlike native ghrelin, ipamorelin shows minimal activity at GHS-R1a populations outside the pituitary, contributing to its selectivity profile.

GHS-R1aGq/11 proteinPLCIP3intracellular Ca2+
02

Somatotroph Calcium Signaling

GHS-R1a activation triggers the Gq/11-PLC-IP3 cascade, releasing calcium from intracellular stores and opening voltage-gated calcium channels. The resulting calcium influx triggers GH vesicle exocytosis. This mechanism is distinct from and synergistic with the cAMP-PKA pathway activated by GHRH.

voltage-gated Ca2+ channelsIP3 receptorsGH secretory vesicles
03

Selective GH Release

Ipamorelin's selectivity is defined by what it does NOT do: unlike GHRP-6 and GHRP-2, it does not significantly stimulate ACTH or cortisol release, and it produces minimal prolactin elevation. This selectivity is attributed to its pentapeptide structure lacking the lipophilic residues that engage off-target receptors.

somatotroph cellsGH release
Evidence-Graded Research Areas

Published Research

Strong
Moderate
Emerging
Preclinical

Growth Hormone Secretion

Strong

Dose-dependent, selective stimulation of GH release demonstrated in multiple species including human subjects. Peak GH levels occur approximately 40 minutes post-administration. GH release is amplified synergistically when co-administered with GHRH or GHRH analogs (e.g., CJC-1295 No DAC), confirming complementary receptor mechanisms.

Bone Metabolism

Moderate

Preclinical and clinical studies demonstrate positive effects on bone mineral content and longitudinal bone growth. GH/IGF-1 axis activation stimulates osteoblast activity and periosteal bone formation. A Phase II clinical trial evaluated ipamorelin for post-operative ileus recovery, with bone effects as secondary endpoints.

Post-Operative Gastrointestinal Recovery

Moderate

Phase II clinical trials evaluated ipamorelin for acceleration of GI recovery following abdominal surgery. Ghrelin receptor agonism in the enteric nervous system promotes gastric motility and intestinal transit, independent of the GH-releasing effects. Results showed trends toward reduced time to first bowel movement.

Body Composition in Aging

Moderate

Age-related GH decline contributes to increased adiposity and decreased lean mass. Ipamorelin's ability to stimulate physiological GH pulses without cortisol or prolactin co-release makes it a candidate for studying GH axis restoration in aging populations without the confounding hormonal effects of less selective secretagogues.

Safety Profile

Ipamorelin has been evaluated in Phase I and Phase II clinical trials with a favorable safety profile. Transient side effects include mild headache, flushing, and injection site reactions. Critically, ipamorelin does not significantly elevate cortisol, ACTH, or prolactin at GH-stimulating doses — a key differentiator from GHRP-6 and GHRP-2. No dose-limiting toxicities reported in clinical studies.

Handling & Storage

Reconstitute with bacteriostatic water. Direct gentle stream along vial wall. Store lyophilized powder at -20°C. Reconstituted solution at 2-8°C, use within 21 days. Peptide is stable in solution at refrigerator temperature.

References & Citations

Peer-Reviewed Literature

  1. 1

    Ipamorelin, the first selective growth hormone secretagogue

    Raun K, Hansen BS, Johansen NL, et al.

    European Journal of Endocrinology, 1998PubMed 9725779DOI
  2. 2

    Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers

    Gobburu JV, Agersø H, Jusko WJ, Ynddal L.

    Pharmaceutical Research, 1999PubMed 10220845DOI
  3. 3

    Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats

    Johansen PB, Nowak J, Skjaerbaek C, et al.

    Growth Hormone & IGF Research, 1999PubMed 10502451DOI
  4. 4

    Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients

    Beck DE, Sweeney WB, McCarter MD, et al.

    International Journal of Colorectal Disease, 2014PubMed 25080924DOI
Frequently Asked Questions

Ipamorelin FAQ

What is Ipamorelin?

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue that selectively activates the GHS-R1a (ghrelin receptor) on pituitary somatotroph cells. It is notable for its selectivity — it stimulates GH release without significantly elevating cortisol, ACTH, or prolactin, distinguishing it from earlier GH secretagogues like GHRP-6.

How does Ipamorelin differ from GHRP-6?

Both are GHS-R1a agonists, but ipamorelin is highly selective for GH release only. GHRP-6 stimulates GH but also increases cortisol, prolactin, and appetite (via ghrelin-like hunger signaling). Ipamorelin's cleaner pharmacological profile is attributed to its distinct pentapeptide structure.

Why combine Ipamorelin with CJC-1295 (No DAC)?

Ipamorelin acts on the GHS-R1a (ghrelin receptor) while CJC-1295 (No DAC) acts on the GHRH receptor. These are separate signaling pathways (Gq/calcium vs. Gs/cAMP) on the same pituitary somatotroph cells. Simultaneous activation produces synergistic GH release exceeding what either compound achieves alone.

How should Ipamorelin be stored?

Store lyophilized powder at -20°C. Reconstitute with bacteriostatic water and refrigerate at 2-8°C. Use reconstituted solution within 21 days.

Has Ipamorelin been used in human clinical trials?

Yes. Ipamorelin was developed by Novo Nordisk and evaluated in Phase I/II clinical trials including studies on GH pharmacokinetics/pharmacodynamics and post-operative ileus. It was the first GH secretagogue to demonstrate selective GH release without cortisol or prolactin co-stimulation in human subjects.

Available for Research

Ipamorelin Products

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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.