Ipamorelin

Ipamorelin is a synthetic pentapeptide built around two non-natural amino acids (Aib at the N-terminus, D-2-naphthylalanine and D-phenylalanine in the core) that binds the growth-hormone-secretagogue receptor — the ghrelin receptor, GHSR-1a — on pituitary somatotrophs ([Raun et al., *Eur J Endocrinol* 1998, 139:552–561](https://doi.org/10.1530/eje.0.1390552)). Receptor agonism triggers a pulsatile release of growth hormone, which drives hepatic IGF-1 production downstream. Mechanistically this differs from Tesamorelin and CJC-1295: those are GHRH analogs binding the GHRH receptor; Ipamorelin mimics ghrelin instead. The pentapeptide structure is also small enough that it crosses some tissue compartments more readily than the larger 44-amino-acid GHRH analogs.

Ipamorelin is the entry-point GH-secretagogue peptide. It earned that role because of a single property documented in the foundational 1998 paper by Raun, Hansen, and colleagues at Novo Nordisk (*European Journal of Endocrinology*): selectivity. Across in vitro and in vivo testing, Ipamorelin produced GH release with potency comparable to GHRH itself, while ACTH, cortisol, prolactin, FSH, LH, and TSH stayed at baseline — even at doses more than 200-fold above the ED50 for GH. Earlier-generation GH secretagogues like GHRP-2 and GHRP-6 raise cortisol and prolactin in parallel with GH, which makes their long-term tolerability story messier; Ipamorelin's selectivity is the reason it became the practitioner default. In practice it is most often combined with a GHRH analog — typically CJC-1295 — on the rationale that the two molecules engage parallel pathways and produce a stronger, more physiological GH pulse than either alone. The combined-stack human evidence is thinner than the single-agent mechanistic data; most of what is published is from small academic studies and the ghrelin-mimetic class as a whole, not from large RCTs of Ipamorelin specifically. Treat the strong selectivity story as well-established mechanistically; treat the body-composition and recovery claims as plausible but undertested in well-controlled human trials.