Research and laboratory use only. Not for human consumption.
Ipamorelin
Ipamorelin is a synthetic five-residue growth hormone secretagogue developed as part of the GHRP research programme. It activates the growth hormone secretagogue receptor, now known as the ghrelin receptor, and was designed to stimulate growth hormone with greater endocrine selectivity than earlier compounds such as GHRP-6 and GHRP-2.
What is Ipamorelin?
Ipamorelin is a synthetic pentapeptide growth hormone secretagogue.
Its sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH2 , containing modified and D-amino-acid residues rather than representing a naturally occurring human peptide sequence.
It was developed during medicinal-chemistry research into growth hormone-releasing peptides and was identified from a series of molecules related to earlier GHRP scaffolds.
Ipamorelin activates the growth hormone secretagogue receptor type 1a , or GHS-R1a, the receptor now recognized as the principal signalling receptor for ghrelin.
Its main pharmacological characteristic is acute stimulation of pituitary growth hormone secretion.
Compared with earlier GHRPs, experimental research found Ipamorelin to be more selective for GH release, particularly with respect to ACTH and cortisol stimulation.
What does the name Ipamorelin mean?
Unlike GHRP-6, the term Ipamorelin is not conventionally expanded as an acronym.
Its scientific identity is therefore best defined by its sequence, receptor pharmacology and developmental code rather than by attempting to assign a literal meaning to each part of the name.
Aib refers to α-aminoisobutyric acid, a non-proteinogenic amino-acid residue.
D-2-Nal is a D-2-naphthylalanine residue, while D-Phe represents D-phenylalanine.
The peptide also has an amidated C-terminus, represented by NH2.
Developed as a selective GH secretagogue
Ipamorelin emerged from a medicinal chemistry programme investigating shorter, more selective growth hormone secretagogue peptides.
Why was Ipamorelin developed?
Earlier growth hormone-releasing peptides such as GHRP-6 and GHRP-2 demonstrated potent GH secretion but were not perfectly selective endocrine stimuli.
Research therefore focused on whether related molecules could retain strong growth hormone activity while reducing stimulation of additional pituitary and adrenal hormones.
Ipamorelin was identified during a major medicinal-chemistry programme at Novo Nordisk.
Published pharmacological work in 1998 described Ipamorelin as the first GHRP-receptor agonist with GH-release selectivity resembling that of GHRH .
The compound later progressed into direct human pharmacokinetic studies and was also investigated as a potential treatment for postoperative ileus.
Amino-acid structure
Ipamorelin is a compact synthetic pentapeptide incorporating several non-standard structural features.
Why is Ipamorelin described as selective?
GHRP-6 and GHRP-2 can stimulate growth hormone effectively, but experimental work also observed increases in ACTH and cortisol.
Ipamorelin was notable because it retained potent GH-releasing activity without producing comparable ACTH or cortisol responses in the original comparative animal studies.
Importantly, the strongest evidence for this hormone selectivity came from preclinical swine studies.
It should therefore not be interpreted as proof that Ipamorelin has no off-target or endocrine effects in humans.
The correct scientific description is that Ipamorelin demonstrated greater GH selectivity than several earlier GHRPs in experimental models .
Why are researchers interested in Ipamorelin?
Its combination of GHS-R activity, measurable human pharmacology and apparent endocrine selectivity made Ipamorelin useful in several areas of experimental research.
Growth Hormone Secretion
Human and animal experiments demonstrate acute stimulation of endogenous GH secretion.
Secretagogue Selectivity
Ipamorelin became useful for studying whether GH secretion could be separated from other endocrine responses produced by earlier GHRPs.
Gastrointestinal Motility
Ghrelin-receptor activity led to preclinical and clinical investigation of Ipamorelin in postoperative ileus.
Bone Biology
Animal studies have examined longitudinal bone growth and bone mineral content after chronic exposure.
How does Ipamorelin work?
Ipamorelin belongs to the growth hormone secretagogue family and acts through ghrelin- receptor signalling rather than through the classical GHRH receptor.
GHS-R1a Activation
Ipamorelin activates the growth hormone secretagogue receptor, the principal signalling receptor for ghrelin.
GH-Axis Signalling
GHS-R pathways in the hypothalamic- pituitary system contribute to stimulation of endogenous GH release.
Pituitary Somatotrophs
Experimental studies demonstrate direct GH release from primary pituitary cells following Ipamorelin exposure.
Gastrointestinal Signalling
The widespread distribution of the ghrelin-receptor system generated interest in possible gastrointestinal promotility effects.
Ipamorelin has direct human PK/PD data
A controlled dose-escalation study evaluated the pharmacokinetics and pharmacodynamics of Ipamorelin in healthy male volunteers.
Eight subjects were studied at each of five intravenous infusion levels.
Drug exposure increased proportionally with dose, and the reported terminal elimination half-life was approximately two hours.
Growth-hormone stimulation appeared as a single episodic release following exposure.
Peak GH occurred at approximately 0.67 hours, followed by an exponential decline toward negligible concentrations.
These findings establish human pharmacokinetic and acute pharmacodynamic activity. They do not establish long-term therapeutic efficacy.
What potential applications have been investigated?
Ipamorelin progressed into human research, but its experimental uses should be distinguished from approved therapeutic applications.
Growth Hormone Secretory Research
Human pharmacology studies established Ipamorelin as a potent stimulus of acute endogenous growth-hormone secretion.
Postoperative Ileus
Because ghrelin-receptor agonism can influence gastrointestinal motility, Ipamorelin progressed into a randomized Phase 2 study in patients undergoing bowel resection.
Bone Growth & Remodelling
Rat studies investigated effects on longitudinal bone growth and bone mineral content, generating hypotheses regarding GH-axis effects on skeletal biology.
Selective GHS Design
Ipamorelin served as a scaffold for subsequent medicinal-chemistry work aimed at developing smaller and orally active secretagogues.
Human evidence showing an acute increase in GH should not be interpreted as proof that Ipamorelin improves muscle growth, recovery, fat loss, athletic performance or healthy ageing. These claims require separate clinical evidence.
How strong is the evidence?
Ipamorelin has substantially more direct human pharmacology than many research peptides, but the evidence for therapeutic efficacy remains limited.
Molecular Pharmacology
Growth hormone secretagogue receptor pharmacology and acute GH release are well characterized.
Animal Evidence
Multiple animal studies investigated GH secretion, bone biology, metabolism and gastrointestinal motility.
Human PK/PD
Human pharmacokinetics and acute GH pharmacodynamics have been directly characterized.
Therapeutic Efficacy
An established therapeutic indication has not been demonstrated.
What has actually been demonstrated in humans?
Human GH release and pharmacokinetics are documented, but long-term therapeutic benefit is not established.
Ipamorelin has been administered directly to humans in controlled research.
The healthy-volunteer pharmacokinetic study demonstrated a clear relationship between Ipamorelin exposure and episodic growth-hormone release.
The study also provided quantitative pharmacokinetic information, including dose proportionality, clearance, volume of distribution and terminal half-life.
A separate Phase 2 proof-of-concept study enrolled patients after bowel-resection surgery to evaluate Ipamorelin as a potential treatment for postoperative ileus.
That study did not show statistically significant improvement in its primary or secondary efficacy endpoints.
Therefore, the available human evidence supports the conclusion that Ipamorelin is pharmacologically active in humans , but does not establish an approved or clinically validated therapeutic use.
The postoperative ileus Phase 2 trial
Ipamorelin progressed beyond endocrine pharmacology into a randomized human trial for postoperative ileus, but the efficacy result was negative.
Postoperative Ileus
Multicenter, double-blind, placebo-controlled Phase 2 proof-of-concept study after small or large bowel resection.
The clinical programme investigated Ipamorelin because activation of the ghrelin receptor can produce gastrointestinal promotility effects.
The randomized study enrolled 117 adults undergoing bowel-resection surgery.
The primary efficacy endpoint was time from the first study dose to tolerance of a standardized solid meal.
Median time was approximately 25.3 hours in the Ipamorelin group and 32.6 hours in the placebo group.
However, the difference was not statistically significant and there were no significant differences in the key secondary efficacy analyses.
The investigators reported that the regimen was generally well tolerated over the short study period, but the trial did not establish clinical efficacy.
FDA's subsequent review noted that the development programme for postoperative ileus was reportedly discontinued after the disappointing efficacy result.
Where is Ipamorelin in the clinical-development process?
Ipamorelin reached direct human pharmacokinetic research and Phase 2 investigation for postoperative ileus, but it did not progress to an approved therapeutic medicine.
Human-studied investigational secretagogue
Ipamorelin is scientifically more advanced than a purely preclinical peptide because it has direct human pharmacology and a completed Phase 2 study.
What don't we know?
Factors affecting Ipamorelin stability
Ipamorelin is a synthetic modified pentapeptide. Stability should be evaluated using documentation for the precise free-base, salt or formulated material under investigation rather than applying a generic storage rule to every form.
Temperature
Temperature can influence chemical degradation and long-term stability of peptide research material.
Moisture
Humidity can affect physical and chemical characteristics of lyophilized peptide preparations.
pH & Solvent
Buffer composition, solvent and pH can influence stability once peptide material is placed in solution.
Chemical Form
Free base, acetate and other formulation forms should be identified explicitly in analytical documentation.
Human-studied investigational growth hormone secretagogue
Ipamorelin has direct human pharmacokinetic and pharmacodynamic evidence and progressed into Phase 2 clinical research for postoperative ileus.
The Phase 2 study did not demonstrate statistically significant clinical efficacy, and the development programme for that indication did not progress to approval.
FDA's current review concludes that available clinical information does not establish effectiveness of Ipamorelin for growth hormone deficiency or postoperative ileus and identifies no approved Ipamorelin drug product.
ASA Research Labs provides this information for scientific and educational purposes only. Nothing on this page should be interpreted as medical advice, dosing guidance or a recommendation for human use.
Selected scientific references
Selected literature covering Ipamorelin's discovery, receptor pharmacology, human pharmacokinetics, skeletal research, gastrointestinal development and regulatory assessment.
Scientific research information only
This profile is provided for scientific and educational information. Ipamorelin has been administered in controlled human research but is not presented by ASA Research Labs as an approved treatment for growth hormone deficiency, muscle growth, recovery, body composition, ageing, gastrointestinal disease or any other medical condition. Demonstration of acute growth-hormone secretion does not establish long-term therapeutic benefit or safety. This page does not provide instructions for administration, dosing or human use.