Ipamorelin is a synthetic pentapeptide which is characterized by releasing potency and efficacy, both in vitro and in vivo. A new outcome of a large-scale chemistry program, Ipamorelin was isolated from a group of compounds which lack the central dipeptide Ala-Trp of the growth  (GHRP)-1. It is a pentapeptide, meaning it is made up of five amino acids, and it works by causing the production of a significant amount  (GH) from the anterior pituitary gland.

Rat Pituitary Cell Assay

Researchers housed groups of 4-8 male albino rats in cages and placed them in rooms with regulated temperature, humidity and light intensity. They then obtained pituitary cell cultures by briefly decapitating the rats and dissecting the pituitaries. The neurointermediate lobes were extracted and the rest of the tissue immediately put in an ice-cold isolation buffer (Gibco) that was supplemented with glucose, non-essential amino acids and 1% BSA, Ph 7.3). The researchers then cut the tissue into fine pieces which were then placed in an isolation buffer that was supplemented with trypsin and DNase.

After incubation for a period of 35-min at room temperature , the tissue was washed in the buffer and then aspirated into single cells. The resultant cell suspension was washed with isolation buffer supplemented with trypsin inhibitor and finally resuspended in culture medium after which the cells were put into microtitre plates and cultured for a period of 3 days at room temperature. After culturing, the cells were washed in stimulation buffer and preincubated for 60 minutes at room temperature. The buffer was exchanged with a new one, after which a test compound solution was added followed by further 15-minute incubation. The medium was then decanted for analysis of released growth hormone.

GHRP-1, TB-500 and GHRP-6 were equipotent in this assay. When the central dipeptide Ala-Trp was removed, there was a slight drop in EC50 but no effect was observed on Emax compared with GHRP-1 which was also studied. When the N-terminal L-Ala was exchanged with D-Ala, there was a more significant decrease in the potency and this time around, a slight drop in Emax was observed.

When L-Ala was replaced with ipamorelin, both EC50 and Emax were brought back to the level of GHRP-1. To understand the pharmacological specificity of Aib (ipamorelin), an investigation had to be carried out to establish whether GHRP antagonists or GHRH had an effect on the stimulation.

These findings are very unique as they prove that GHRP-2 and GHRP-6 can cause an increase in ACTH and in the levels of cortisol plasma too. This means, therefore, that that GHRP-2 and GHRP-6 cannot to be regarded as selective GH secretagogues. Secondly, ipamorelin is similar to GHRH in the effect it has on plasma levels.

In conclusion, ipamorelin, displayed GHRP receptor agonist profile, just like GHRP-6 when observed in vitro. As the first GHRP receptor-active GH secretagogue with this quality, ipamorelin does hold great promise and potential.