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Pharmacological profile of a new orally active growth hormone secretagogue, SM-130686

Study · animal · The Journal of endocrinology · 2001 · DOI 10.1677/joe.0.1710481 · PMID 11739014

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This study in cultured rat pituitary cells and rats evaluated SM-130686, a novel orally active growth hormone secretagogue structurally distinct from prior compounds like MK-677. The authors reported that SM-130686 stimulated GH release from rat pituitary cells in a dose-dependent manner and inhibited binding of a labeled ligand to the human GHS receptor 1a, acting through the GHS receptor pathway. A single 10 mg/kg oral dose increased plasma GH in anesthetized rats, peaking at 20-45 min. Repeated oral dosing of 10 mg/kg twice daily for 9 days was associated with increased body weight and fat free mass, and elevated serum IGF-I. In vitro GH-releasing activity relative to ghrelin was about 52%, leading the authors to describe SM-130686 as a partial agonist for the GHS receptor.

Abstract

SM-130686, an oxindole derivative, is a novel orally active GH secretagogue (GHS) which is structurally distinct from previously reported GHSs such as MK-677, NN703 and hexarelin. SM-130686 stimulates GH release from cultured rat pituitary cells in a dose-dependent manner. Half-maximum stimulation was observed at a concentration of 6.3+/-3.4 nM. SM-130686-induced GH release was inhibited by a GHS antagonist, but not by a GH-releasing hormone antagonist. SM-130686 dose-dependently inhibited the binding of radiolabeled ligand, (35)S-MK-677, to human GHS receptor 1a (IC(50)=1.2 nM). This indicates that SM-130686 stimulates GH release through the GHS receptor. The effect of a single oral administration of SM-130686 on GH release in pentobarbital-anesthetized rats was studied. After treatment with 10 mg/kg SM-130686, plasma GH concentrations measured by radioimmunoassay significantly increased, reaching a peak at 20-45 min, and remained above baseline during the experimental period (60 min). The anabolic effect of repetitive SM-130686 administration was studied in rats. Rats received 10 mg/kg SM-130686 orally twice a day and were weighed every day for 9 days. At day 9 there was a significant increase in both the body weight and the fat free mass (19.5+/-2.1 and 18.1+/-7.5 g respectively). Serum IGF-I concentration was also significantly elevated 6 h after the last dose of SM-130686. An endogenous GHS ligand for the GHS receptor has recently been identified from stomach extract and designated as ghrelin. The GH-releasing activity in vitro relative to ghrelin (100%) was about 52% for SM-130686. It is likely that SM-130686 is a partial agonist for the GHS receptor. In summary, we describe here an orally active GHS, SM-130686, which acts through the GHS receptor. Repetitive administration of SM-130686 to rats, similar to repetitive administration of GH, significantly increased the fat free mass by an amount almost equal to the gain in body weight.

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