Tag Archive for growth hormone secretagogue

Ipamorelin Basics

Ipamorelin

Ipamorelin Basics

Ipamorelin




Ipamorelin or NNC 26-0161, a polypeptide hormone, is a growth hormone secretagogue and ghrelin mimetic and analog developed by Novo Nordisk[3]. Ipamorelin belongs to the most recent generation of GHRPs from the mid 1990s and causes significant release of growth hormone by itself, due both to its suppression of somatostatin (an antagonist to GHRH) and stimulation of release of GH from the anterior pituitary, similar to GHRP-2 and GHRP-6 which are compounds from the same class (growth hormone releasing peptides).[1] The cells that produce and release GH are known as somatotropes.[2] Like GHRP-2, ipamorelin does not have ghrelin’s lipogenic properties. Like GHRP-2 and unlike GHRP-6 ipamorelin never induces hunger in mammals. Ipamorelin acts synergistically when applied during a native GHRH (growth-hormone releasing hormone) pulse or when coadministered with GHRH or a GHRH analog such as Sermorelin or GRF 1-29 (growth releasing factor, aminos 1-29).[1] The synergy comes both due to the suppression of somatostatin and the fact that ipamorelin increases GH release per-somatotrope, while GHRH increases the number of somatotropes releasing GH.[1,2] There is also a secondary effect of neuronal excitation in the hypothalamus caused by ipamorelin, which lasts for approximately 3 hours after application, similar to GHRP-2 and GHRP-6.




Ipamorelin has a unique property among the GHRP class of peptides. That property is known as selectiveness. Raun et al demonstrated the selectiveness of ipamorelin for GH release only in a study:  The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, 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 swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (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 FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.[3]

Whereas GHRP-6 and GHRP-2 cause a release and increase in cortisol and prolactin levels, ipamorelin only selectively releases GH at any dose. Further, a mega-dose of ipamorelin results in a concomitant mega-release of GH (up to the entire amount present in the pituitary), whereas GHRP-2 and GHRP-6 have limits of approximately 1mcg/kg in humans for their maximal GH release.[4,5]  Cititations:  [1] Bowers CY, Momany F, Reynolds GA. In vitro and in vivo activity of a small synthetic peptide with potent GH releasing activity. 64th Annual Meeting of the Endocrine Society, San Francisco, 1982, p. 205.  [2]Bowers CY, Momany F, Reynolds GA, Sartor O. Multiple receptors mediate GH release. 7th International Congress of Endocrinology, Quebec, Canada, 1984, p. 464.  [3] Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61.  [4] Brosnan-Cook, M. et al. (1998) Iontophoretic delivery of ipamorelin, a growth hormone secretagogue. Proceedings of 80th Annual Meeting Endocrine Society, New Orleans, USA. Abstract Pp1-186.  [5] Jogarao V S Gobburu; Henrik Agerso; William J Jusko . Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide in Human Volunteers. Lars Ynddal Pharmaceutical Research: Sep 1999; 16, 9; ProQuest Nursing & Allied Health Source p. 1412.

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