Ipamorelin

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue: Aib-His-D-2-Nal-D-Phe-Lys-NH2. It was described in 1998 as the first selective member of its class, releasing growth hormone through a secretagogue receptor rather than the growth hormone releasing factor receptor (Raun et al., 1998).

The endogenous ligand of that receptor was identified a year later as ghrelin, an acylated peptide from the stomach (Kojima et al., 1999). Ipamorelin has been studied in cell culture, rats, swine and human pharmacology and clinical trials.

Because ipamorelin holds non-natural residues, it is not a fragment of any human protein.

Published work on ipamorelin falls into five areas. Each summary below states the model used.

Selectivity in the founding study

Ipamorelin was identified within a series that removed the central Ala-Trp dipeptide of an earlier secretagogue. In primary rat pituitary cells it released growth hormone with potency similar to GHRP-6, and antagonist profiling placed its action at a secretagogue-like receptor rather than the releasing factor receptor.

It released growth hormone in rats and in conscious swine. The result that defined it was a negative one: in swine it did not raise ACTH or cortisol above the levels seen with the releasing factor, while GHRP-6 and GHRP-2 both did (Raun et al., 1998). Models: rat cell culture, rats and swine.

Two receptors, two mechanisms

The secretagogue class and the releasing factor act through separate pathways. In rat primary pituitary cell culture, a hexapeptide secretagogue and the releasing factor produced a synergistic effect on growth hormone release at maximal concentrations; the secretagogue alone did not raise intracellular cyclic AMP while the releasing factor raised it roughly three fold, and the two did not cross-desensitize (Cheng et al., 1989). That finding, made with an earlier secretagogue, is the cell-culture basis for research designs that pair the two classes. Model: rat cell culture.

Longitudinal bone growth in rats

In adult female rats, ipamorelin produced a graded increase in longitudinal growth rate across three treatment levels measured by tetracycline labelling in the proximal tibia, from 42 to 52 micrometres per day, with no change in total IGF-I or in serum markers of bone turnover (Johansen et al., 1999). Model: rat.

Human pharmacokinetics

A study at five escalating levels in healthy male volunteers reported kinetics proportional to the amount given, a terminal half-life of about two hours, and a single episode of growth hormone release peaking near 40 minutes (Gobburu et al., 1999). Model: healthy human volunteers.

A completed clinical trial

Ipamorelin has been tested in a finished randomized controlled trial. In a double-blind, placebo-controlled phase 2 study in 114 adults after bowel resection, it was well tolerated but produced no significant difference from placebo in time to tolerance of a standardized solid meal, 25.3 hours against 32.6 (Beck et al., 2014). Model: phase 2 clinical trial.