MK-677 is a potent, orally active growth hormone (GH) secretagogue with EC50 value of 1.3nM for releasing GH from rat pituitary cells in culture. Addition of 10nM MK-677 elicited transient elevations of cytosolic free calcium through the activation of L-type Ca2+ channels in rat somatotrophs. MK-677 at concentration of 0.1μM greatly potentiated the effect of GHRH (10nM) on GH release and the accumulation of intracellular cAMP in the pituitary cell assay. Elevation of GH could be observed in dogs after oral doses of MK-677 as low as 0.125mg/kg, without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg.
体内研究
Ibutamoren Mesylate (MK-677) is a potent, non-peptide agonist of the Growth Hormone Secretagogue Receptor (GHSR) and is effective when taken orally. It functions primarily as a growth hormone (GH) secretagogue[1].
In a study involving dogs, daily administration of Ibutamoren Mesylate at 5 mg/kg resulted in statistically significant increases in both body weight and serum levels of IGF-1 and GH. However, this treatment did not significantly alter IGF-1 or GH levels in the cerebrospinal fluid (CSF) on either day 7 or 15 of the study[1].
Pre-treatment of mice with GH inhibits the activation of arcuate neurons by Ibutamoren Mesylate (50 μg, intraperitoneally). In knockout mice, neither GH nor octreotide blocks the activation of arcuate neurons by Ibutamoren Mesylate, indicating a specific interaction pathway that is GH-dependent[2].
Chronic oral administration of MK-0677 leads to significant and sustained increases in both GH and IGF-I levels throughout the treatment period. The GH increases are episodic, rising above baseline levels after each administration of MK-0677[3].
MK-0677, when administered orally or intravenously, causes significant increases in peak GH concentrations. This demonstrates its effectiveness as a GH secretagogue, capable of inducing rapid, substantial, and enduring elevations in GH levels[4].
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