Ipamorelin
Also known as: NNC 26-0161
A highly selective pentapeptide growth hormone secretagogue and ghrelin receptor agonist studied for clean, pulsatile GH release.
Molecular Data
- Class
- Pentapeptide / Growth hormone secretagogue (GHRP)
- Molecular Weight
- 711.85 Da
- Molecular Formula
- C₃₈H₄₉N₉O₅
- Half-Life
- ~2 hours (estimated, animal data)
- Sequence / Structure
- Aib-His-D-2-Nal-D-Phe-Lys-NH₂
Mechanism of Action
Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) that acts as a selective agonist at the growth hormone secretagogue receptor (GHS-R1a), the same receptor targeted by the endogenous hormone ghrelin. In preclinical research it has been characterized as one of the most selective growth hormone releasing peptides (GHRPs) identified:
- Stimulates pulsatile GH release from pituitary somatotrophs by activating GHS-R1a, mimicking the GH-releasing action of ghrelin without acting on the GHRH receptor.
- High selectivity for GH — unlike earlier GHRPs such as GHRP-2 and GHRP-6, ipamorelin does not meaningfully elevate prolactin, ACTH, or cortisol at effective doses in animal models, making it a clean research probe of the GH axis.
- Does not stimulate appetite to the degree of ghrelin or GHRP-6 in most rodent studies, allowing GH-axis effects to be dissociated from feeding behavior.
- Synergizes with GHRH analogs (e.g. CJC-1295) in research settings, where combined GHS-R and GHRH-receptor activation produces a larger GH pulse than either agent alone.
Its short half-life and lack of receptor desensitization at physiological doses have made ipamorelin a widely used reference GHRP in secretagogue research.
Research History
Ipamorelin was developed in the late 1990s by researchers at Novo Nordisk as part of a program to identify growth hormone secretagogues with improved selectivity over first-generation GHRPs. It was first described in a 1998 paper by Raun et al. in the European Journal of Endocrinology, which characterized its potency and its notably clean endocrine profile relative to GHRP-2 and GHRP-6.
Subsequent preclinical work examined ipamorelin's effects on GH pulse amplitude, IGF-1 levels, bone mineral content, and body composition in rodent models. Its selectivity — releasing GH without significant prolactin or cortisol elevation — made it a preferred tool compound for isolating GHS-R1a signaling in the hypothalamic-pituitary axis.
Although ipamorelin advanced into early clinical investigation for post-operative ileus, it was not developed into an approved drug. As of 2024 it remains an unapproved research compound, and its effects in humans outside of limited early-phase studies are not established. The majority of the evidence base is preclinical.
Notable Studies
Ipamorelin, the first selective growth hormone secretagogue
1998Raun K, Hansen BS, Johansen NL, et al. · European Journal of Endocrinology
Foundational characterization of ipamorelin, demonstrating potent GH release with high selectivity and no significant increase in ACTH or cortisol, distinguishing it from earlier GHRPs.
Growth hormone secretagogues stimulate the hypothalamic-pituitary-adrenal axis and are diabetogenic in the Zucker diabetic fatty rat
1999Johansen PB, Nowak J, Skjærbæk C, et al. · European Journal of Endocrinology
Compared endocrine effects of several secretagogues in a rodent model, further documenting ipamorelin's relatively selective GH-releasing profile.
The effect of growth hormone secretagogue ipamorelin on gastrointestinal transit and postoperative ileus in rats
2007Venkova K, Fraser G, Hoveyda HR, Greenwood-Van Meerveld B · Neurogastroenterology & Motility
Examined ipamorelin's prokinetic effects on GI transit in a rodent post-operative ileus model, part of the rationale for its early clinical investigation in that indication.
Research Protocols
The following protocols describe doses used in published research studies. They are not prescriptions or recommendations for human use.
Rodent GH-release studies
- Dose
- 3–100 µg/kg
- Route
- Subcutaneous or intravenous
- Frequency
- Single-dose or once daily
- Duration
- Acute to 14 days
Dose range spanning published rodent secretagogue experiments; these are animal research doses and are not established for human use.
Rodent bone and body-composition studies
- Dose
- ~0.5 mg/kg/day
- Route
- Subcutaneous
- Frequency
- Once or twice daily
- Duration
- Up to 12 weeks
Longer-duration protocols used to assess IGF-1, bone, and body-composition endpoints in animal models.