Infos about MK-677
Type: Orally active growth hormone secretagogue
Mol. mass: 528.662 g/mol
Half life: ~24h
MK-677 is an orally active nonpeptide spiropiperidine previously demonstrated to be functionally indistinguishable in vitro and in vivo from GH-releasing peptide, a relatively selective GH secretagogue. MK-677 enhances the pulsatile release of GH, resulting in sustained elevations in IGF-I, and is well tolerated after oral administration in animals, healthy young men, and older men and women.
Growth hormone secretagogue MK-677: no clinical ef... [Neurology. 2008] - PubMed result
Results: Administration of MK-677 25 mg resulted in a 60.1% increase in serum IGF-1 levels at 6 weeks and a 72.9% increase at 12 months.
Effects of an oral ghrelin mimetic on body composi... [Ann Intern Med. 2008] - PubMed result
Results: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.
MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism
Results: In summary, we observed in this short-term study that oral administration of MK-677 reverses the protein catabolism caused by dietary caloric restriction. These data suggest that MK-677 may be useful as adjunctive therapy in certain catabolic states. MK-677 produced a peak GH response of 55.9 ng/ml after the first dose (day 8) and 22.6 ng/ml after a week of dosing (day 14) compared with peak GH responses of approximately 9 ng/ml (day 8) and approximately 7 ng/ml (day 14) with placebo (P < 0.05 for both comparisons). The degree of GH stimulation observed appears to be sufficient to improve nitrogen balance under the stress of caloric restriction. Whether the short-term anabolic effects observed in our volunteers apply also to patients who are catabolic because of certain acute or chronic disease states remains to be established. Future studies should attempt to determine whether the anabolic effects of MK-677 will persist with prolonged treatment, and whether they will be associated with clinical benefits, such as shorter hospital stay and accelerated convalesence.
Treatment of obese subjects with the oral growth h... [J Clin Endocrinol Metab. 1999] - PubMed result
Results: In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.
The effects of MK-0677, an oral growth hormone sec... [J Am Geriatr Soc. 2004] - PubMed result
Results: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.
Results: The primary results, except for BMD, are provided for month 12. MK-677, with or without alendronate, increased insulin-like growth factor I levels from baseline (39% and 45%; P < 0.05 vs. placebo). MK-677 increased osteocalcin and urinary NTx by 22% and 41%, on the average, respectively (P < 0.05 vs. placebo). MK-677 and alendronate mitigated the reduction in bone formation compared with alendronate alone based on mean relative changes in serum osteocalcin (−40% vs. −54%; P < 0.05, combination vs. alendronate) and reduced the effect of alendronate on resorption (NTx) as well (−52% vs. −61%; P < 0.05, combination vs. alendronate). MK-677 plus alendronate increased BMD at the femoral neck (4.2% vs. 2.5% for alendronate).
MK-677 is generally well tolerated based on a review of patient discontinuations and serious adverse events. GH-mediated side effects were noted in the groups receiving MK-677, although adverse events resulting in discontinuation from the study were relatively infrequent. There were reports of fluid retention, for example, in groups receiving MK-677. These reports included weight gain and edema/swelling. Body weight increased 2–3 kg in groups receiving MK-677, whereas there was no significant change from baseline body weight in patients who received placebo.
Elevations in serum glucose or PRL resulted in discontinuation in three patients each (all received MK-677). Modest increases in serum PRL (within the physiological range) and in fasting blood glucose were noted in patients who received MK-677, consistent with earlier experience with MK-677. Clinically significant increases in serum transaminase values (>3 times the upper limit of normal) resulted in study discontinuation in two patients (both received MK-677). There were no other significant differences among treatment groups in laboratory values.
Common dosage is 25mg ed