Ipamorelin

Ipamorelin (CAS 170851-70-4) is a synthetic pentapeptide with sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 (711.9 Da), belonging to the Growth Hormone Releasing Peptides (GHRP) family. Developed by Novo Nordisk in the 1990s (Raun 1998, Eur J Endocrinol), it stands out from analogues (GHRP-2, GHRP-6, hexarelin) by exceptional selectivity for the GHS-R1a (ghrelin) receptor, without detectable activity on hypothalamic-pituitary-adrenocortical (HPA), gonadotropic or lactotropic axes.

Mechanism of action. Ipamorelin activates the GHS-R1a receptor (class A GPCR, Gαq coupling → PLC → IP3/DAG → intracellular Ca²⁺) expressed predominantly in the anterior pituitary, hypothalamus and to a lesser extent pancreas and intestine. Activation induces GH release from somatotrope granules, without concomitant ACTH/cortisol, FSH/LH or prolactin stimulation — a unique pharmacological profile within GHRPs. Plasma half-life is approximately 2 hours in rats.

Synergy with GHRH. Ipamorelin combination with a GHRH analogue (CJC-1295 with or without DAC, sermorelin, tesamorelin) produces supra-additive synergy of 5-10x on GH release, through intracellular convergence of cAMP (GHRH-R Gαs coupling) and Ca²⁺ (GHS-R1a Gαq coupling) pathways and relief of somatostatin feedback inhibition. This stack is used in research to maximise pulsatile GH peak while preserving physiological pulsatility.

Preclinical models. Ipamorelin has been evaluated in models of osteoporosis (ovariectomy/OVX), cancer cachexia (C26), postoperative ileus (Helsinn HD-13 and HD-14 phase II studies, Eur J Pharmacol), juvenile growth retardation and muscle frailty in the elderly. The favourable safety profile (absence of cortisol elevation) makes it a preferred tool for GH/IGF-1 axis studies. Lab Peptides France markets RUO ipamorelin in 5mg and 10mg vials, with an HPLC ≥ 98% specification.