MK-677 is a long-acting agonist of the ghrelin receptor and stimulates the production of human growth hormone (GH). This spiroindoline sulfonamide is also known as Ibutamoren, MK-677, L-163,191 and was formerly referred to as Oratrope.

In a study conducted by Jacks et al., published in Endocrinology in 1997, 8 beagles were administered doses of MK-677 of 0.25 mg/kg. This resulted in GH levels being 5.3 times higher than the original baseline levels. At a dose of 0.5 mg/kg, GH levels increased 9 times, and at a dose of 1 mg/kg, they increased almost 16 times (15.8 times the baseline value). It's important to emphasize that these doses were administered orally, rather than via intravenous or intramuscular injection.

The insulin-like growth factor remained elevated by 30% for 8 hours, indicating that MK-677 is a long-acting compound, at least in beagles. GH levels also remained elevated for up to 6 hours. The authors of the study noted that cortisol levels also increased but to a lesser extent than GH levels.

MK-677 is not just a GH secretagogue but also an orally active agonist of the ghrelin receptor. This means that it has an effect on ghrelin receptors. Zhang et al. explain that the "hunger hormone" ghrelin activates the ghrelin receptor (GHSR) to stimulate food intake and GH release, as well as to regulate reward signaling.

Besides its role in signaling hunger, it also influences various other physiological processes including stress, glucose metabolism, body weight, cognition, intestinal motility, food craving, adiposity, and even pain perception.

An extensive study by Zhang and his team on the chemical structure of MK-677 showed that this compound mimics the first four N-terminal residues of ghrelin, including the octanoyl group that binds to the lower region of the ligand-binding pocket. More details can be found in their research paper: Link to paper

For more information on the various target organs of ghrelin, see the following image: Link to image

In another study, published in the International Journal of Molecular Sciences, Jeong et al. administered MK-677 to mice genetically predisposed to overproducing amyloid beta-peptide (Aβ). This protein is responsible for the plaques and tangles observed in the brains of Alzheimer's patients. The mice received MK-677 injections for ten days at doses of 0.1, 1, and 3 mg/kg. The last two groups showed increased food intake, especially at the 3 mg/kg dose. However, at the end of the ten days, there was no significant difference in body weight between the different dosage groups.

The study showed that treatment with MK-677 resulted in reduced Aβ deposition, fewer neuronal and synaptic losses, and reduced glial changes in the cortical layers of the brain. Furthermore, the researchers concluded that MK-677 also reduced neuroinflammation and neurodegeneration associated with Aβ.