Compound reference
Ipamorelin
The first selective growth-hormone secretagogue — it releases GH in pulses without raising cortisol or prolactin. Its one real clinical program (post-operative ileus) failed, and it is unapproved, prohibited in sport, and a gray-market staple.
- CAS
- 170851-70-4
- Formula
- C38H49N9O5
- Molar mass
- ≈711.9 g/mol
- Sequence
- Aib-His-D-2-Nal-D-Phe-Lys-NH2
- Half-life
- About 2 hours
Research peptide; not FDA-approved as a drug.
Mode of action
Ipamorelin is a synthetic pentapeptide and a selective agonist of the ghrelin receptor (GHS-R1a) in the pituitary and hypothalamus. Activating that receptor triggers a pulse of growth-hormone (GH) release, which in turn raises IGF-1.
Its defining feature is selectivity. Earlier growth-hormone-releasing peptides — GHRP-6, GHRP-2, hexarelin — also raise cortisol, prolactin, or ACTH. Ipamorelin was the first GHS-R agonist to release GH cleanly, without meaningfully moving those other hormones, which is why it became the preferred GHRP. It works through a different receptor than the GHRH analogues (sermorelin, CJC-1295), so the two classes are synergistic: combining a GHRP with a GHRH analogue produces a larger GH pulse than either alone — the rationale behind the popular CJC-1295 + ipamorelin pairing.
Main intended effect
Pulsatile GH release, and the downstream IGF-1 rise — explored clinically for catabolic and gastrointestinal conditions, and used off-label (gray-market) for body composition, recovery, and "anti-aging."
Areas of interest
The legitimate clinical interest centred on GH-axis modulation and, most concretely, post-operative ileus. The far larger interest today is gray-market: ipamorelin is one of the most-searched peptides, almost always stacked with CJC-1295, marketed for muscle, fat loss, sleep, and recovery — uses that have not been tested in controlled human trials.
Evidence for intended effects
The pharmacology is well established; the clinical payoff is not. Early human studies confirmed that ipamorelin releases GH selectively and characterised its roughly two-hour pharmacokinetics, and the GHRP/GHRH synergy is documented. Its furthest-developed indication was post-operative ileus, taken into a Phase 2 dose-finding program — which did not meet its primary clinical endpoint, and development did not continue. There are no controlled human trials supporting the body-composition or anti-aging uses it is actually sold for, and reviews note that human efficacy data are largely lacking.
| Strand | What exists | Tier |
|---|---|---|
| Selective GH release | Phase 1 + PK/PD human studies | Established pharmacology |
| Post-operative ileus | Phase 2 dose-finding | Negative on primary endpoint |
| Body composition / anti-aging | Marketed use | No controlled human data |
| Bone / metabolic | Rodent models | Preclinical |
Studied amounts (literature dosing context)
Human studies dosed ipamorelin intravenously or subcutaneously to characterise GH release and pharmacokinetics, and the post-operative ileus program ran its own dose-finding. Those are trial amounts from programs that did not lead to approval; there is no approved dose, and this page does not provide dosing guidance.
Safety and regulatory status
Acutely, ipamorelin is well tolerated, and its clean hormonal profile (no meaningful cortisol or prolactin rise) was a selling point. Long-term human safety, however, is essentially unstudied — and as a growth-hormone secretagogue it raises the same theoretical concerns as GH itself around glucose handling and tumour growth.
On regulation it is firmly outside approved use: the FDA placed ipamorelin in an interim Category 2 (significant safety risks) and barred it from compounding, the World Anti-Doping Agency prohibits it (athletes have been sanctioned), and it is sold as a research compound. Independent testing of directly-marketed peptides found a large fraction failing basic purity and content benchmarks, with some endotoxin contamination — so what is sold as "ipamorelin" is frequently not what the label claims.
Sources
Ipamorelin, the First Selective Growth Hormone Secretagogue
Original pharmacological characterization by Raun and colleagues (Novo Nordisk, Eur J Endocrinol, 1998) describing ipamorelin, a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) derived from GHRP-1. In vitro and in vivo studies across rodent and swine models demonstrated potent GH release with an ED50 of 2.3 nmol/kg in conscious swine and maximal plasma GH of 65 ng/ml. In contrast to GHRP-6 and GHRP-2, ipamorelin did not elevate ACTH or cortisol even at doses 200-fold above the GH threshold, and had no significant effect on prolactin, FSH, LH, or TSH. The authors characterised ipamorelin as the first GHRP-receptor agonist with hormonal selectivity comparable to GHRH, supporting its candidacy for clinical development with a reduced off-target endocrine risk profile.
Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males
Narrative review examining the role of growth hormone secretagogues, including ipamorelin, as adjuncts to testosterone replacement therapy in hypogonadal males with metabolic concerns affecting body composition. The authors situate GH secretagogues within the broader endocrine rationale for managing GH deficiency alongside androgen deficiency, discussing how agents acting at ghrelin receptors can augment lean mass and reduce adiposity through pulsatile GH stimulation. Mechanistic discussion covers the GH/IGF-1 axis, age-related GH decline, and the selectivity advantages of peptide secretagogues over exogenous GH. The review is primarily narrative and lacks head-to-head clinical trial data, limiting evidence-graded conclusions about comparative efficacy or long-term safety.
Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Cryo-EM structural study (Liu and colleagues) resolving high-resolution complexes of the human ghrelin receptor (GHSR) coupled to Gi protein in the presence of either the endogenous ligand ghrelin or the synthetic agonist ibutamoren (MK-677). The structures defined the agonist-binding pocket, identified a critical salt bridge and aromatic cluster near the binding site as activation motifs, and revealed how ghrelin's octanoyl group and ibutamoren occupy partially overlapping but distinct interaction regions to drive the same receptor active state. Functional validation in cells expressing wild-type and mutant GHSR confirmed the structural inferences via calcium mobilization assays. The study characterizes the molecular target shared by all growth-hormone secretagogues, including ipamorelin, though the study itself involves ghrelin and ibutamoren rather than ipamorelin directly. Clinical translation of structural insights requires additional pharmacological and efficacy studies.
Ipamorelin, a new growth-hormone-releasing peptide, induces dose-dependent increases in growth hormone in healthy volunteers
Phase 1 single ascending dose study of ipamorelin in healthy male volunteers, evaluating dose-dependent growth hormone release, selectivity profile, and tolerability. The trial demonstrated dose-dependent GH secretion across the dose range tested and notably reported no significant changes in cortisol or prolactin at GH-stimulating doses, distinguishing ipamorelin from earlier GHRPs that elevated cortisol and prolactin at higher doses. These selectivity data were a primary basis for advancing ipamorelin into Phase 2 gastrointestinal motility trials. The study established the acute GH-stimulatory and safety profile that characterizes ipamorelin's pharmacology in humans.
Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin in Healthy Volunteers
Phase I dose-escalation PK/PD study (Gobburu and colleagues, Pharm Res 1999) in healthy male volunteers (n = 8 per dose level) receiving five intravenous infusion rates of ipamorelin (4.21, 14.02, 42.13, 84.27, and 140.45 nmol/kg) over 15 minutes. Pharmacokinetics were dose-proportional with a terminal half-life of 2 hours, clearance of 0.078 L/h/kg, and volume of distribution at steady-state of 0.22 L/kg. A single GH release episode peaked at 0.67 hours post-infusion, with half-maximal stimulatory concentration (SC50) of 214 nmol/L and a maximal GH production rate of 694 mIU/L/h; GH then declined exponentially to negligible levels. Inter-individual variability was greater for pharmacodynamic than pharmacokinetic parameters. The authors concluded that the PK/PD model provides a useful characterization of ipamorelin disposition and GH response across the dose range studied.
Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone
Foundational human study (Bowers and colleagues, JCEM 1990) in 18 normal adult men evaluating intravenous bolus doses of the synthetic hexapeptide GHRP (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) at 0.1, 0.3, and 1.0 µg/kg alone and in combination with GHRH 1.0 µg/kg. GHRP produced dose-dependent peak serum GH levels: 7.6 ± 2.5 µg/L (0.1 µg/kg), 16.5 ± 4.1 µg/L (0.3 µg/kg), and 68.7 ± 15.5 µg/L (1.0 µg/kg) versus 1.2 ± 0.3 µg/L for placebo; co-administration with GHRH produced synergistic GH release exceeding either agent alone. Prolactin and cortisol rose approximately twofold only at the highest GHRP dose; mild facial flushing occurred in 16 of 18 subjects receiving GHRH. The study establishes the two-receptor rationale for GHRH-analog and ghrelin-mimetic stacking, though it uses an early GHRP hexapeptide rather than ipamorelin and does not examine CJC-1295.
Phase 2 Randomized Trial of Ipamorelin for Postoperative Ileus
Multicenter, double-blind, placebo-controlled Phase 2 trial (NCT00672074; Beck and colleagues, Int J Colorectal Dis 2014) in 114 adults undergoing small or large bowel resection via open or laparoscopic surgery, randomized to IV ipamorelin 0.03 mg/kg or placebo twice daily from postoperative day 1 through day 7 or hospital discharge. The primary endpoint was time to tolerance of a standardized solid meal; median time was 25.3 hours with ipamorelin versus 32.6 hours with placebo (p = 0.15), a non-significant difference. Treatment-emergent adverse events occurred in 87.5% of the ipamorelin group and 94.8% of the placebo group, indicating the drug was well tolerated. Despite the favorable safety profile, the lack of statistically significant efficacy over placebo for postoperative ileus led to halting further development of this indication.
Phase 2 Dose-Finding Study of Ipamorelin for Recovery of Gastrointestinal Function After Bowel Resection (NCT01280344)
Phase 2, randomized, double-blind, placebo-controlled dose-finding trial (NCT01280344) evaluating intravenous ipamorelin at three dosing regimens — 0.03 mg/kg twice daily, 0.06 mg/kg twice daily, and 0.06 mg/kg three times daily — versus placebo for recovery of gastrointestinal function after small or large bowel resection with primary anastomosis. The trial was completed and its registry record documents that the formal Helsinn/Æterna Zentaris clinical program for ipamorelin was directed entirely at postoperative gastrointestinal motility, not body composition or growth hormone augmentation. Results from this dose-finding study informed the design of the subsequent Phase 2 efficacy trial (NCT00672074) that ultimately failed to meet its primary endpoint.
The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats
Twelve-week subcutaneous infusion study (Svensson and colleagues) in 13-week-old female Sprague-Dawley rats comparing ipamorelin (0.5 mg/kg/day), GHRP-6 (0.5 mg/kg/day), and recombinant GH (3.5 mg/kg/day) administered via osmotic minipumps, with in vivo DXA measurements every four weeks. All three active treatments increased total body weight and total tibial and vertebral bone mineral content (BMC) compared with vehicle controls; however, when corrected for body weight, total BMC showed no significant difference between groups. Post-mortem analysis established that the cortical BMC gain resulted from expanded bone dimensions (increased periosteal apposition) rather than elevated volumetric mineral density. This mechanistic distinction — dimensional growth rather than true mineralization enhancement — is relevant when interpreting reported bone-protective claims. All findings are in young adult female rats; applicability to males, aged animals, or humans requires further study.
FDA Statement on Ipamorelin Safety and Regulatory Status
FDA regulatory page (July 2023) evaluating ipamorelin free base and ipamorelin acetate for use in compounded drug preparations administered by subcutaneous injection. The FDA states that no adequate human safety data exist for compounded ipamorelin and identifies specific concerns including potential immunogenicity arising from peptide impurities, inadequate characterization of the active pharmaceutical ingredient, and an absence of well-controlled clinical trials supporting safety or efficacy. Both salt forms are addressed, and neither holds FDA approval in any dosage form. The document reflects the FDA's determination that the identified safety gaps are unresolved and that compounding of ipamorelin presents significant risk to patients.
https://www.fda.gov/drugs/human-drug-compounding/ipamorelin-free-base-and-ipamorelin-acetate
FDA Category 2 and Withdrawn-Nomination Status for Ipamorelin and CJC‑1295
FDA regulatory page, current as of April 22, 2026, listing bulk drug substances that may present significant safety risks under the compounding framework. Ipamorelin acetate is placed in Category 2 under the 503B outsourcing facility interim policy and is also listed in the nominated-but-withdrawn section for 503A, reflecting that its 503A nomination was withdrawn following adverse evaluation. CJC-1295 appears among nominated-but-withdrawn substances, with FDA-cited concerns encompassing immunogenicity, peptide-related impurities, inadequate active pharmaceutical ingredient characterization, reports of serious adverse events, and a limited clinical evidence base. Pharmacy Compounding Advisory Committee records corroborate votes against placing both ipamorelin and CJC-1295 bulk drug substances on the 503A Bulks List. The collective result is that neither substance may be lawfully compounded under 503A or 503B as of this listing.
WADA Prohibited List 2026 — Ipamorelin as a Growth Hormone Secretagogue
The World Anti-Doping Agency (WADA) 2026 Prohibited List, approved September 2025 and in force from 1 January 2026, is an International Standard that governs anti-doping eligibility in all sports under the World Anti-Doping Code. Ipamorelin is explicitly named as an example compound under class S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics), specifically within the growth hormone secretagogue subcategory. S2 substances are prohibited at all times, both in-competition and out-of-competition, and are classified as non-specified substances, meaning the evidentiary threshold for sanctions is higher than for specified substances. No therapeutic use exemption is available for ipamorelin given the absence of any approved therapeutic indication. A positive test carries a presumptive four-year ban under the WADA Code.
https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
USADA Doping Sanction Involving Ipamorelin (David Branch)
USADA sanction notice announcing a two-year doping ban for UFC mixed martial artist David Branch (Montville, N.J.), effective July 26, 2019, following detection of ipamorelin in an out-of-competition urine sample collected May 24, 2019. Ipamorelin is classified as a growth hormone secretagogue and is prohibited at all times under the WADA Prohibited List category "Peptide Hormones, Growth Factors, Related Substances, and Mimetics." The two-year penalty reflects the standard sanction for a non-Specified Substance under the UFC Anti-Doping Policy. USADA additionally noted that ipamorelin lacks FDA approval for human use. This case is a concrete anti-doping enforcement example confirming ipamorelin's prohibited status in competitive sport.
https://www.usada.org/sanction/david-branch-receives-doping-sanction/
Evaluation of Research Grade Peptides Marketed Directly to Consumers Reveals Extensive Variability in Purity and Measured Abundance
Analysis (Mendias and Awan, preprint, 2026) of 6,441 gray-market peptide samples across fourteen compounds — including ipamorelin, BPC-157, CJC-1295, GHK-Cu, PT-141, retatrutide, semaglutide, sermorelin, TB-500, tesamorelin, and tirzepatide. Applying two quality-acceptance frameworks, between 41.6% and 71.1% of samples failed to meet basic quality criteria, and about 15% showed measurable endotoxin contamination. The study quantifies how often directly-marketed "research grade" peptides miss purity and content benchmarks — a central safety concern for any non-pharmaceutical source.