What is Ipamorelin?

Compound Spotlight

Ipamorelin is five amino acids long and was designed to do one thing. Earlier growth hormone releasing peptides raised growth hormone, but they also pushed up ACTH and cortisol. Ipamorelin was the first compound in the class reported to release growth hormone with a selectivity close to that of the body’s own releasing hormone, and that single property explains most of the interest in it.

Where it comes from

In the 1980s and 1990s, several groups built small synthetic peptides that released growth hormone through a pathway separate from growth hormone releasing hormone (GHRH)., among them GHRP-6, GHRP-1 and GHRP-2. They were potent, but they were not clean: they also stimulated the stress axis.

Novo Nordisk ran a chemistry programme to find something better. Ipamorelin emerged from a series of compounds built by removing the central Ala-Trp dipeptide from GHRP-1, leaving a five-residue molecule with several non-standard amino acids (Aib, D-2-naphthylalanine and D-phenylalanine). Raun and colleagues published its pharmacology in 1998 under the title “Ipamorelin, the first selective growth hormone secretagogue.”

The receptor, and a hormone found afterwards

The order of discovery here is backwards. The synthetic secretagogues came first. In 1996 Howard and colleagues cloned the receptor they act on, a G-protein-coupled receptor in the pituitary and hypothalamus, and concluded that the drugs were probably mimicking a hormone nobody had found yet. In 1999 Kojima and colleagues found it: a 28-amino-acid acylated peptide from the stomach, which they named ghrelin.

So when ipamorelin was characterized, its target was simply called a “GHRP-like receptor.” Using GHRP and GHRH antagonists, Raun’s group showed that ipamorelin works through the same GHRP-like receptor as GHRP-6, not through the GHRH receptor. That receptor is now known as GHS-R1a, or the ghrelin receptor. This is why ipamorelin is described today as a ghrelin mimetic, and why the gut became a research interest later on, since ghrelin-receptor signalling also affects gastrointestinal motility.

What “selective” actually meant

In rat pituitary cells and anaesthetised rats, ipamorelin released growth hormone with potency and efficacy similar to GHRP-6. The selectivity work was done in conscious swine. None of the secretagogues tested (ipamorelin, GHRP-6, GHRP-2) changed FSH, LH, prolactin or TSH. GHRP-6 and GHRP-2 raised ACTH and cortisol. Ipamorelin did not raise them to levels significantly different from those seen after GHRH, and this held even at doses more than 200-fold above its ED50 for growth hormone release.

That is a clean result, but it is a result in pigs. The authors’ conclusion was that ipamorelin’s selectivity for growth hormone release was similar to GHRH’s. The endocrine profile in humans over longer exposure was not established by this paper.

What has been studied in people

The main published human pharmacology is a 1999 study by Gobburu and colleagues in healthy male volunteers. Across five dose levels, ipamorelin’s pharmacokinetics were dose-proportional, with a terminal half-life of about two hours. Each dose produced a single episode of growth hormone release that peaked at roughly 40 minutes (0.67 hours) and then declined to negligible levels.

Development then moved toward the gut. In rats with surgically induced postoperative ileus, Venkova and colleagues reported that ipamorelin shortened the time to first bowel movement after a single dose, and that repeated dosing increased faecal output, food intake and body-weight gain over 48 hours.

That led to a human trial. Beck and colleagues ran a multicentre, double-blind, placebo-controlled phase 2 proof-of-concept study in 114 evaluable adults after bowel resection, with ipamorelin given in hospital for up to seven days. The key endpoint was time to tolerating a solid meal. The median was 25.3 hours with ipamorelin and 32.6 hours with placebo, a difference that was not statistically significant (p = 0.15). The authors reported no significant differences between ipamorelin and placebo on the key or secondary efficacy analyses. No phase 3 programme followed in the published literature.

What the evidence supports

The strongest evidence is pharmacological. Ipamorelin is a well-characterized ghrelin-receptor agonist that releases growth hormone in rats, swine and humans. Its selectivity over ACTH and cortisol is shown in swine. In humans, it is known to produce a short, single pulse of growth hormone.

Outcome evidence is thin. In rats, studies have reported effects on gut motility and, in one 15-day study in adult female rats, a dose-dependent increase in longitudinal bone growth without a change in total IGF-I. But the one sizeable human efficacy trial, in postoperative ileus, did not meet its endpoints. There are no published controlled trials showing that ipamorelin improves body composition, recovery or any other outcome in people. The gap between “raises growth hormone” and “produces a measurable benefit” remains open, as it does for most of this class.

Frequently asked questions

Is ipamorelin the same as ghrelin?

No. Ghrelin is a 28-amino-acid hormone made mainly in the stomach. Ipamorelin is a synthetic five-residue peptide that acts on the same receptor. It was developed before ghrelin was even discovered.

Why is it so often paired with a GHRH analogue?

Because the two act on separate receptors. Ipamorelin works through the ghrelin receptor, while GHRH analogues such as CJC-1295 or sermorelin work through the GHRH receptor. Our growth hormone secretagogue overview covers this combination logic, and our CJC-1295 and Ipamorelin breakdown looks at the pairing directly.

Did ipamorelin fail in clinical trials?

In postoperative ileus, its phase 2 trial did not show a statistically significant benefit over placebo. That trial tested gut recovery after surgery, not growth hormone effects, and it was described by its authors as small. It is the most advanced published clinical test of the compound.

How do I know what is actually in the vial?

Every lot we sell has a published Certificate of Analysis from an independent, third-party lab confirming identity and purity. Lot numbers on the vial should match the COA you are referencing.

References

• Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552–561.
• Howard AD, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974–977.
• Kojima M, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660.
• Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999;16(9):1412–1416.
• Johansen PB, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999;9(2):106–113.
• Venkova K, et al. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009;329(3):1110–1116.
• Beck DE, et al. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014;29(12):1527–1534.

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For laboratory and research use only. Not for human consumption. Ipamorelin is not approved as a medicine by any regulatory authority. This article summarizes published research for informational purposes and is not medical advice, nor a recommendation or protocol for use.

Related research compounds

Arc Peptides supplies these compounds, each third-party tested for purity and identity with a lot-specific Certificate of Analysis:

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For laboratory research use only. Not for human consumption.