GHRP-6 vs Ipamorelin

How GHRP-6 and Ipamorelin differ

GHRP-6 and Ipamorelin are different molecules. GHRP-6 is a synthetic six-residue peptide with a free N-terminal amine and a C-terminal amide. Ipamorelin is a synthetic five-residue peptide that does not correspond to any natural peptide sequence. Two of GHRP-6's six residues are D-configured, and it carries two tryptophans. Ipamorelin contains non-natural and D-configured amino acids, including alpha-aminoisobutyric acid and a D-configured naphthylalanine.

In the literature reviewed for GHRP-6, the human data come from acute studies. Registry searches return no registered interventional trials for it.^[1] An author of the 1990 human study of GHRP-6 held an inventor interest.^[7] The literature reviewed for GHRP-6 reports no serious safety finding from its human studies.

The literature reviewed for Ipamorelin includes two published human studies. One was an early-phase pharmacokinetic-pharmacodynamic study in healthy male volunteers.^[2] The other was a randomized phase 2 trial of 114 participants, in one indication, and it missed its key endpoint and its secondary analyses.^[3] Almost everything else known about Ipamorelin comes from preclinical pharmacology. Much of the defining preclinical work on Ipamorelin comes from its original developer, which raises the usual question of independent replication. The literature reviewed for Ipamorelin reports no serious safety finding from its human studies.

The FDA has not approved either GHRP-6 or Ipamorelin for human use.

Neither peptide contains cysteine, methionine, asparagine, glutamine or aspartate, so in each the degradation routes that dominate most peptides are closed. What remains in GHRP-6 is oxidation of its two tryptophan indoles, driven by air, light and trace metals. In Ipamorelin, the remaining routes are general. Its amide bonds hydrolyze under strong acid or alkali, slowly near neutral pH, and its aromatic side chains oxidize far more slowly than a tryptophan does. Each is cationic and carries aromatic rings, so each can adsorb to surfaces both electrostatically and hydrophobically. In each, mass spectrometry cannot verify the configuration of the D-residues, since a D-residue and its L-form are identical in mass.

Have GHRP-6 and Ipamorelin been compared directly?

A 1998 study tested GHRP-6 and Ipamorelin in conscious swine.^[4] The paper came from Ipamorelin's developer.^[4] A 2000 study tested each in young adult female rats.^[5] A 2001 study tested each in mice.^[8] A 2002 study tested each in vitro, in pituitary cell cultures from young female rats given one of three pretreatments.^[9] A 2009 study tested each in a rat surgical model.^[10] Results are reported for each compound in each paper.