Ipamorelin explained: why a 1998 paper called it the first selective growth hormone secretagogue

What it is. Ipamorelin (NNC 26-0161) is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, about 712 daltons. It is an agonist at GHS-R1a, the receptor later identified as the ghrelin receptor. It has no natural counterpart; it came out of a structure-activity program at Novo Nordisk that started from the GHRP-1 scaffold and dropped the central Ala-Trp dipeptide of the earlier hexapeptides.

The defining paper. Raun and colleagues, European Journal of Endocrinology, 1998. In rat pituitary cells and conscious swine, ipamorelin released growth hormone with potency comparable to GHRP-6, but did not significantly change ACTH, cortisol, prolactin, LH, FSH or TSH at concentrations more than 200-fold above those needed for GH release. That is why the paper is titled "the first selective growth hormone secretagogue." Earlier GHRPs had been reported to co-release ACTH, cortisol and prolactin.

Mechanism, briefly. GHS-R1a is a class A GPCR that signals mainly through Gq and phospholipase C, with IP3-driven calcium release as the proximate trigger for GH exocytosis (Yin et al., Int J Mol Sci, 2014). Why ipamorelin is selective at the receptor level is still an open question in the literature.

vs GHRP-6. Same receptor, same lineage. GHRP-6 is the 1984 Bowers hexapeptide (about 873 Da). Johansen et al. (Xenobiotica, 1998) reported ipamorelin's plasma clearance in rats was several-fold lower than GHRP-6's.

Regulatory. Never approved by the FDA or EMA. One published phase 2 human trial (Beck et al., 2014). Reviewed by the FDA's compounding advisory committee in 2024.

Full write-ups:

• https://spartalabs.net/us/blog/ipamorelin-research-overview
• https://spartalabs.net/us/blog/ipamorelin-mechanism-of-action
• https://spartalabs.net/us/blog/ghrp-6-vs-ipamorelin

Sparta Labs sells ipamorelin as a research reference material with per-lot COAs: https://spartalabs.net/us/products/ipamorelin

Research use only. Not for human consumption. Nothing here is medical advice.