Description
FOR RESEARCH PURPOSES ONLY
The first selective growth hormone secretagogue to be used in clinical settings is ipamorelin peptides. GHRH and ipamorelin growth hormone are pentapeptides with comparable preferences for GH release. IPA is available for research use at Peptides Canada Direct.
The 1st selective growth hormone secretagogue.
K Raun, NL Johansen, BS Hansen, H Thogersen, M Ankersen, PH Andersen Department of GH Biology, K Madsen, Novo Nordisk A/S, Malov, Denmark.
This article outlines the pharmacology and development of ipamorelin, a new and dynamic growth hormone (GH) secretagogue. Ipamorelin, a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), demonstrates exceptional GH-releasing efficacy and potency both in vivo and in vitro. Discovered through an extensive chemistry program, ipamorelin emerged from a group of compounds that lack the central dipeptide Ala-Trp found in growth hormone-releasing peptide (GHRP)-1.
Ipamorelin released growth hormone from primary rat pituitary cells in vitro with the same potency and utility as GHRP-6 (ECs = 1.3+/-0.4nmol/l, Emax = 85+/-5% vs. 2.2+/-0.3nmol/l and 100%). A pharmacological profiling with growth hormone-releasing hormone (GHRH) antagonists and GHRP showed that ipamorelin, comparable to GHRP-6, increases GH release via a GHRP-like receptor.
In pentobarbital anaesthetised mice, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious pigs, ipamorelin released Emax = 65+/-0.2 ng GH/ml plasma and GH with an ED50 = 2.3+/-0.03 nmol/kg. This was again very comparable to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma).
GHRP-2 displayed lower efficacy but higher potency (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected LH, FSH, TSH or PRL plasma levels. When GHRP-2 and GHRP-6 were administered, cortisol and ACTH plasma levels rose. Surprisingly, ipamorelin did not significantly increase ACTH or cortisol levels compared to those experienced after GHRH stimulation. This lack of effect on cortisol plasma levels and ACTH was evident even at doses more than 200-fold higher than the ED50 for GH release.
In short, ipamorelin is the first GHRP-receptor agonist with discernment for GH release comparable to that displayed by GHRH. The specific nature of ipamorelin makes this compound a very interesting candidate for future clinical development.