Ipamorelin, the first selective growth hormone secretagogue

This seminal article introduced ipamorelin as the first truly selective growth hormone (GH) secretagogue, differentiating it from other peptides of the same class such as GHRP-6 and hexarelin. The study was conducted using in vitro and in vivo models in rats and swine to characterize the complete pharmacological profile of the peptide.

The results demonstrated that ipamorelin released GH in a dose-dependent manner with potency comparable to GHRP-6, but with a crucial difference: it did not cause significant elevation in levels of cortisol, ACTH, or prolactin, even at doses up to 100 times higher than the effective dose for GH release. This selectivity was unprecedented among GH secretagogues known at the time.

The mechanism of action involves binding to the GH secretagogue receptor (GHS-R), but in a way that does not activate the hypothalamic-pituitary pathways responsible for cortisol and prolactin release. This pharmacological specificity confers ipamorelin a significantly superior safety profile compared to other GHRPs.

This study established ipamorelin as the benchmark for a new generation of GH secretagogues with lower risk of unwanted hormonal side effects, making it particularly attractive for long-term clinical applications where selective stimulation of the GH axis is desired.