August 29, 2026 · 2 min read

Ipamorelin: the first selective growth hormone secretagogue, and what selective meant

How ipamorelin releases growth hormone through a GHRP-like receptor without raising cortisol, per the original pharmacology and a rat bone study.

Ipamorelin is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, that stimulates the release of growth hormone (GH). It belongs to the family of GH secretagogues, which act on a receptor distinct from the one used by GHRH. The original 1998 paper describing it was titled "the first selective growth hormone secretagogue," and the word selective is the point.

The ipamorelin sequence

Sequence: alpha-Aminoisobutyric acid, Histidine, D-2-Naphthylalanine, D-Phenylalanine, Lysine.

  • Modified residue
  • Positively charged
Length
5 residues, 3 of them modified
Average mass
711.9 Da
Formula
C38H49N9O5
Aib-His-D-2-Nal-D-Phe-Lys-NH2, as given in the original 1998 paper (Raun et al.). The mass calculated from this structure matches PubChem (CID 9831659).

Potency in swine

In vitro, ipamorelin released GH from primary rat pituitary cells with potency and efficacy similar to GHRP-6, and experiments with GHRP and GHRH antagonists showed it acts through a GHRP-like receptor. In anesthetized rats and conscious swine it released GH at doses comparable to GHRP-6. GHRP-2 was more potent but less efficacious.

Dose for half-maximal GH release in conscious swine

  • GHRP-20.6 nmol/kg
  • Ipamorelin2.3 nmol/kg
  • GHRP-63.9 nmol/kg
ED50 values from Raun et al., Eur J Endocrinol 1998. A lower value means greater potency. Ipamorelin was similar to GHRP-6 and less potent than GHRP-2 on this measure.

What selective meant

The earlier secretagogues GHRP-6 and GHRP-2 raised ACTH and cortisol along with GH. Ipamorelin did not, and the authors described this as a very surprising result. None of the compounds tested changed FSH, LH, prolactin or TSH. That specificity is what earned the name.

Hormones measured in the swine experiments

  1. Growth hormone

    Released by ipamorelin, as intended.

  2. ACTH and cortisol

    GHRP-6 and GHRP-2 raised them. Ipamorelin did not differ significantly from GHRH stimulation.

  3. FSH, LH, prolactin, TSH

    Unaffected by any of the secretagogues tested.

From Raun et al., Eur J Endocrinol 1998. This is a summary of the published findings in swine.

Later animal work

A 2001 study in adult female rats gave methylprednisolone, ipamorelin or both for three months. In the combination group, muscle tetanic tension was significantly higher and the periosteal bone formation rate was four times higher than with the glucocorticoid alone. A 2024 study in ferrets looked at ipamorelin and anamorelin on cisplatin-induced weight loss.

All of this is animal work. We found no large controlled trials of ipamorelin in people, so what it does there remains an open question.

References

  1. Raun K et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol 1998.
  2. Andersen NB et al. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res 2001.
  3. Lu Z et al. The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets. Physiol Behav 2024.

Related research notes