What Is Ipamorelin? The Selective GH Secretagogue

Ipamorelin is a synthetic pentapeptide that stimulates growth hormone (GH) release through the ghrelin receptor (GHSR). Novo Nordisk scientists described it in 1998 as “the first selective growth hormone secretagogue”. In swine it released GH without the rises in ACTH and cortisol seen with older GH-releasing peptides (Raun et al., 1998). Its short human half-life, about 2 hours, gives pulse-like GH responses.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH₂; 711.9 g/mol.
Ghrelin-receptor (GHSR) agonist, derived from the GHRP-1 series.
Potency and efficacy for GH release similar to GHRP-6 in rat and swine models.
Selective: no significant ACTH or cortisol release in swine; no effect on FSH, LH, prolactin or TSH.
Human terminal half-life about 2 hours.

Quick facts

Property	Value
Sequence	Aib-His-D-2-Nal-D-Phe-Lys-NH₂
Non-natural residues	Aib (aminoisobutyric acid), D-2-naphthylalanine, D-phenylalanine
Formula / weight	C₃₈H₄₉N₉O₅, 711.9 g/mol
Receptor	Growth hormone secretagogue receptor (GHSR-1a)
Human half-life	~2 h (terminal)

Our ipamorelin research peptide is supplied in 5 mg and 10 mg vials with lot-level HPLC and MS data.

The ghrelin receptor

GHSR is expressed mainly in the pituitary and brain. It regulates GH secretion as well as food intake, adiposity and glucose homeostasis. Unusually, it has constitutive (ligand-independent) activity that can be increased by ghrelin and reduced by the endogenous peptide LEAP2 (Cornejo et al., 2021). Synthetic GH secretagogues such as ipamorelin act on this receptor, a different pathway from GHRH analogues such as CJC-1295 and tesamorelin.

Discovery and selectivity

Ipamorelin came out of a chemistry programme that removed the central Ala-Trp dipeptide of GHRP-1 (Raun et al., 1998). The key pharmacology results:

Model	Ipamorelin	GHRP-6
Rat pituitary cells, EC₅₀	1.3 nmol/L (E_max 85%)	2.2 nmol/L (E_max 100%)
Anaesthetised rats, ED₅₀	80 nmol/kg	115 nmol/kg
Conscious swine, ED₅₀	2.3 nmol/kg	3.9 nmol/kg
ACTH / cortisol in swine	Not significantly different from GHRH	Increased

Antagonist profiling confirmed that ipamorelin, like GHRP-6, acts through a GHRP-type receptor rather than the GHRH receptor. GHRP-2 was more potent but less efficacious and also raised ACTH and cortisol. None of the secretagogues changed FSH, LH, prolactin or TSH. This selectivity profile is the reason ipamorelin became a reference compound for “clean” GHSR-mediated GH release in research.

Human pharmacokinetics

A dose-escalation study in healthy men infused ipamorelin at five rates over 15 minutes (eight subjects per level). Pharmacokinetics were dose-proportional, with a terminal half-life of about 2 hours, clearance of 0.078 L/h/kg and volume of distribution of 0.22 L/kg. Each infusion produced a single GH episode peaking at about 0.67 hours, then declining to negligible levels. In the PK/PD model, the concentration needed for half-maximal GH stimulation was 214 nmol/L (Gobburu et al., 1999).

Ipamorelin in combination research

Because GHSR and GHRH receptor signalling converge on GH release, ipamorelin is often studied with a GHRH analogue. See CJC-1295 + ipamorelin and tesamorelin vs ipamorelin.

How ipamorelin compares with other GH secretagogues

Peptide	Length	GH release	ACTH/cortisol (swine)
GHRP-6	6 aa	Potent	Increased
GHRP-2	6 aa	More potent, lower efficacy	Increased
Ipamorelin	5 aa	Similar to GHRP-6	Not significantly different from GHRH

Data from Raun et al., 1998. Hexarelin and GHRP-2/-6 are also available as research peptides for comparative work.

Handling in the lab

Store lyophilized powder at −20 °C, sealed and dark.
Readily water-soluble; reconstitute with bacteriostatic or sterile water (method).
Store solutions at 2–8 °C; avoid repeated freeze–thaw.
Small molecule-like size (712 Da) makes MS identity checks straightforward.
Calculate concentrations with the peptide reconstitution calculator.

Open questions

Does ipamorelin’s ACTH/cortisol selectivity, shown in swine, hold to the same degree in other species?
How do GHSR constitutive activity and LEAP2 levels modify responses to ipamorelin in different physiological states?
How does repeated exposure affect GHSR responsiveness over time? Ipamorelin-specific data on this in humans are limited.
Does ipamorelin influence appetite through GHSR in the brain, as ghrelin does? This has not been characterised in the human studies published so far.

Related research

Frequently asked questions

What is ipamorelin?

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) that stimulates growth hormone release through the growth hormone secretagogue receptor (GHSR), the receptor for ghrelin.

Why is ipamorelin called selective?

In the original pharmacology study in swine, ipamorelin released GH without raising ACTH or cortisol beyond levels seen after GHRH, whereas GHRP-6 and GHRP-2 increased both. It also did not affect FSH, LH, prolactin or TSH.

What is the half-life of ipamorelin?

About 2 hours (terminal half-life) in healthy male volunteers, with dose-proportional pharmacokinetics.

How does ipamorelin differ from CJC-1295?

They act on different receptors. Ipamorelin is a ghrelin-receptor (GHSR) agonist; CJC-1295 is a GHRH-receptor agonist. Because the two pathways converge on GH release, they are often studied together.

What is ipamorelin's molecular weight?

About 711.9 g/mol (C38H49N9O5).

References

Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998. PMID: 9849822 https://pubmed.ncbi.nlm.nih.gov/9849822/
Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999. PMID: 10496658 https://pubmed.ncbi.nlm.nih.gov/10496658/
Cornejo MP, et al. The ups and downs of growth hormone secretagogue receptor signaling. FEBS J. 2021. PMID: 33460513 https://pubmed.ncbi.nlm.nih.gov/33460513/
PubChem Compound Summary for CID 9831659, Ipamorelin. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/9831659