General Pharmacology of KP-102 (GHRP-2), a Potent Growth Hormone-Releasing Peptide

Abstract

The general pharmacological effects of the hexapeptide KP-102 (D-alanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide dihydrochloride, growth hormone-releasing peptide-2, GHRP-2, pralmorelin, CAS 158861-67-7), which potently promotes growth hormone (GH) release by acting at both hypothalamic and pituitary sites, were evaluated in various animal experimental models. The administration of KP-102 showed no obvious effect at a pharmacological dose on the central nervous system. KP-102 had no significant effect on the autonomic nervous system and smooth muscle except a slight and transient increase in spontaneous motility of isolated rabbit ileum and contraction of isolated guinea pig ileum at high doses. There was negligible effect on the respiratory and cardiovascular systems, digestive system, renal function and blood system after KP-102 treatment. These results suggest that KP-102 has no serious general pharmacological effects at dose levels showing GH-releasing activity in the experimental animals. Therefore, it is concluded that KP-102 will be a useful drug for the diagnosis of serious GH deficiency and for treatment of short stature.

Beneficial Effects of Growth Hormone-Releasing Peptide on Myocardial Oxidative Stress and Left Ventricular Dysfunction in Dilated Cardiomyopathic Hamsters

“…Although more detailed studies are needed to define the appropriate dose of GHRP-2, Furuta et al reported that GHRP-2 has no serious side-effects at dose levels that induce GH-releasing activity. 21 …”

GH-releasing Peptide-2 does not Stimulate Arginine Vasopressin Secretion in Healthy Men

“…the reason for this may be that GhRp-2 might have a different effect on AVp secretion independent of osmolality and hemodynamic factors, unlike ghrelin, probably because GhRp-2 is an exogenous ligand that binds the GhS receptor, while ghrelin is an endogenous ligand that binds the GhS receptor [2]. this difference supports the notion that, for Acth secretion, GhRp-2 acts via cRF [7], while ghrelin acts via AVp [12], and ghrelin stimulates secretion of gastric juice with gastrin, whereas GhRp-2 has no such effects [23]. Moreover, AVp levels increase significantly with the itt [17][18][19].…”

Growth hormone secretagogues: history, mechanism of action, and clinical development

“…Although pralmorelin reached Phase II clinical trials for the treatment of short statue, further development was discontinued. This was presumably because pralmorelin failed to increase plasma GH levels sufficiently in patients with GHD …”

“…Pralmorelin, also known as GHRP2, is an orally active, short‐acting, synthetic peptide that was originally developed by Polygen in Germany and Tulane University in the USA and then acquired by Kaken Pharmaceutical Company in Japan . In rats, pralmorelin was associated with two‐fold to three‐fold increase in GH release compared with GHRP6 after intravenous administration.…”

“…This was presumably because pralmorelin failed to increase plasma GH levels sufficiently in patients with GHD. 19 Macimorelin A Phase III clinical trial has shown that oral macimorelin was effective for the diagnosis of adult GHD with 82% sensitivity and 92% sensitivity at an optimal GH cut point of 2.7 ng/ mL, which was comparable with GHRH and arginine test. 65 Another Phase III clinical trial has been completed in 2016, to compare its efficacy with the insulin tolerance test (ClinicalTrial.gov Identifier: NCT02558829), and AEterna Zentaris announced to pursue approvals of macimorelin for this indication by the FDA and the European Medicines Agency in March 2017.…”