GHRP-6 vs Ipamorelin

GHRP-6

GHRP-6 is a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, and one of the earliest growth hormone-releasing peptides to be described. It came out of structure-activity work on small synthetic peptides, carried out before anyone knew which receptor they acted on. That receptor, GHS-R1a, was later shown to respond to ghrelin, a hormone made mainly in the stomach, so GHRP-6 is now classed as a ghrelin receptor agonist. It has been used in pituitary cell and receptor assays, in a large body of animal work, and in human endocrine studies of hormone secretion. Because the same receptor takes part in the control of feeding, it has also served as a tool in appetite research.

Ipamorelin

Ipamorelin is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, that acts as an agonist at the ghrelin receptor, GHS-R1a. It was derived from earlier growth hormone-releasing peptides and is one residue shorter than GHRP-2 and GHRP-6. What set it apart in the original animal pharmacology was selectivity: growth hormone release was not accompanied by the rises in ACTH and cortisol recorded for older compounds in the class. Because ghrelin receptors are also present in the gut, it has been examined in rodent models of gastrointestinal motility, and it has been the subject of a small number of human clinical studies. Human data remain limited, and most of what is known comes from animal work.

How GHRP-6 acts

GHRP-6 is reported to bind and activate GHS-R1a, a G protein-coupled receptor that signals mainly through Gq, phospholipase C and intracellular calcium. On pituitary somatotrophs this signalling triggers growth hormone release. The receptor is also expressed in the hypothalamus, including on neuropeptide Y and agouti-related peptide neurons of the arcuate nucleus, which rodent studies have linked to the control of food intake; that distribution is the basis for the peptide's use in feeding research. Small increases in ACTH, cortisol and prolactin have been reported with it in addition to growth hormone. Interactions with somatostatin signalling have been proposed but are less clearly defined.

How Ipamorelin acts

Ipamorelin has been reported to bind GHS-R1a on somatotroph cells of the anterior pituitary, where receptor activation raises intracellular calcium and triggers growth hormone secretion. Its reported selectivity concerns other pituitary and adrenal hormones: in the animal studies that first characterised it, ACTH and cortisol did not rise appreciably, unlike with GHRP-6 or GHRP-2. The structural basis for this difference has not been fully explained. The receptor is also found in the gut wall and its nerve supply, which is the rationale for rodent studies of gastrointestinal transit using this compound.

The records side by side

• Type: GHRP-6, Growth hormone secretagogue (GHRP); Ipamorelin, Growth hormone secretagogue (GHRP)
• Length: GHRP-6, 6 amino acids; Ipamorelin, 5 amino acids
• Molecular weight: GHRP-6, 873.0 g/mol; Ipamorelin, 711.9 g/mol
• Molecular formula: GHRP-6, C46H56N12O6; Ipamorelin, C38H49N9O5

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.