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Ibutamoren (Mesylate), (MK-677, Oratrope, L-163191)
USD $64.95
Concentration
Form
Size
25mg
Solid
40
WARNING: This product is not for human or veterinary use.
In stock
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CAS# | 159752-10-0 |
UNII | R90JB6QJ2B |
EINECS | N/A |
Molecular Formula | C27H36N4O5S•CH3SO3H |
Formula Weight | 624.8 |
Purity | 99% |
Solubility | |
Stability | ≥ 2 years |
InChIKey | DUGMCDWNXXFHDE-VZYDHVRKSA-N |
Pubchem Compund ID | https://pubchem.ncbi.nlm.nih.gov/compound/6450830 |
Synonyms | L-163, L-163191, Mesylate, MK-0677, MK-677, MK677, Oratrope, Receptor Modulators, SARM |
Storage | Room Temperature |
Shipping | Room Temperature |
What is Ibutamoren / Mk-677?
MK-677, also known as Ibutamoren, is an orally-active spiropiperidine that stimulates the natural production of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) [a] [e]. It has attracted interest from the medical community due to its potential positive effects on body composition, especially bone mineral density and also the ratio of lean mass to adipose tissue. Studies have reported beneficial effects for elderly patients recovering from hip fractures [g], and also suggest that it may improve quality of sleep [m]. Other studies suggest that it helps alleviate GH deficiency, both in adults [k] and in children [u].
Modes of Action (How Does MK-677 work?)
MK-677 is a nonpeptide ghrelin receptor agonist and pulsatile GH secretagogue. Both in vitro and in vivo, it was found in 1995 to be mechanistically indistinguishable from the peptide GH secretagogue GHFP-6 [a]. Human studies have shown it to be selective. One 2008 study found that prolonged administration only caused a slight increase in cortisol levels, while raising raising elderly subjects’ GH concentrations in blood plasma to levels normally only seen in young people [b]. Another 1996 study found that only 7 days of administration caused an increase in plasma IGF-1 levels and also in GH pulse frequency, with no statistically significant increase in cortisol levels either in plasma or in urinary excretions [f].
Ibutamoren Benefits/ Effects
Researchers have found MK-677 to have the following beneficial effects in humans:
- Builds Muscle
A two month clinical trial in 1998 found that MK-677 caused a sustained decrease in the body fat percentage of obese patients [c].
- Prevents Muscle Wasting
MK-677 was found in 1998 to reverse a catabolic state caused by caloric restriction [d]. In 2008 it was also found to reverse age-related decline in lean body mass [b]. A review of the literature conducted in 2019 suggests that ghrelin agonists such as MK-677 may have an important role to play in sarcopenia treatment [s].
- Increases Bone Density
One 1998 study in young obese males found statistically significant increases in markers of bone formation after only two weeks of treatment with MK-677. In particular, the increase in procollagen III peptide levels was highly significant (p = 0.001 vs. placebo). After 8 weeks of treatment, MK-677 also caused rises in serum levels of osteocalcin, a marker whose presence is associated with the formation of osteoblasts [h]. Another 1999 study found MK-699 improved osteocalcin levels in elderly adults. Significant effects were found in both healthy and functionally impaired subjects [j]. When post-menopausal female osteoporosis patients were treated with MK-677 together with alendronate, after one year they were found to have higher osteocalcin levels compared to a control group who received alendronate alone. After 18 months they were found to have higher bone mineral density (FMD) at the femoral neck. This study was reported in 2001 [i].
- Improves Sleep Quality
It is well known that there is a relationship between sleep and GH secretion [n][o], and also that ghrelin promotes slow-wave sleep [r]. This has prompted research into whether MK-677 may improve the quality of sleep. A 1996 study of both young adults suggested that daily administration of 25mg doses of MK-677 may improve sleep quality [q]. This was replicated in 1997 with not only a group of young adult subjects, but also another group of elderly adults. This study not only confirmed the results in young adults, but also suggested that MK-677 may alleviate the difficulty that elderly people have in getting sufficient sleep [m].
- May Promote Longevity
MK-677 may increase the human lifespan by reducing obesity [c], reversing sarcopenia [d],[b][s], and alleviating the loss of bone density associated with osteoporosis [i].
- Combats Growth Hormone Deficiency
A 1996 study of elderly men and women found that 25mg doses of oral MK-677 restored their GH levels to those of young people after 4 weeks of daily administration [e]. This was followed up in 1997 with a rising dose study (10-50 mg/day) of adults with GH deficiency, which found improvements in both GH and IGF-1 concentrations [k]. Subsequently, a 2001 study in GH deficient children found that MK-677 could increase the levels of GH, IGF-1 and IGF‐binding protein 3 [u].
- May Support Injury Recovery
One 2011 clinical trial of elderly hip fracture patients found that MK-677 caused statistically significant improvements in a number of areas. These included gait speed and IGF-1 levels [g].
Animal Studies
A 1995 study in dogs found that MK-677 increased the levels of GH when administered both intravenously and orally [a]. A 1996 study in beagles found that an intact pituitary gland was necessary for MK-677 to raise the levels of GH and IGF-1 [t].
Side Effects / Toxicity
Increased Appetite
A number of human studies (conducted in 2004 and 2005) have reported increases in appetite after ghrelin administration [v][w], and one 2008 human clinical trial reported this after administration of MK-677 [b].
Possible higher congestive heart failure rate
A 2011 human clinical trial with elderly subjects was terminated prematurely due to a higher incidence of congestive heart failure in the treatment group compared with the placebo group [g].
Short-Lived Increases in Cortisol and Prolactin
Two human clinical trials reported that MK-677 triggered increases in cortisol and prolactin in some patients [c][d].
Musculoskeletal Pain and Fluid Retention
Two 1998 clinical trials reported that a small portion of subjects complained of musculoskeletal pain and swelling, however they reported that this was mild and short-lived and did not discontinue the study [j][b].
Dosage / Half life
In all of the human studies, MK-677 was taken orally once per day. By far the most common dose was 25mg/day [b][c][d][e][f][g][h][i][m][q]. The study that investigated the treatment of osteoporosis using MK-677 in combination with alendronate also gave this dosage of MK-677 [i]. A 1999 study reported that MK-677 increased bone density 25mg/day was taken orally for two weeks, after which the dose was increased to 50mg/day [j]. One 1996 study reported an increase in GH and IGF-1 levels from daily oral doses of 10mg, but found no significant effects from 2mg/ day [f]. However another 1996 study found statistically significant increases in GH and IGF-1 from both 25mg/day and 5mg/day dosing regimens [q]. A 1997 study found MK-677 to be beneficial for GH deficient adults when given in orally in doses of 10mg/day, and also 50mg/day [k]. The study that investigated the use of MK-677 for GH deficient children gave daily doses of 0.8mg/kg [u].
References
[a] Patchett, A. A., et al. “Design and Biological Activities of L-163,191 (MK-0677): a Potent, Orally Active Growth Hormone Secretagogue.” Proceedings of the National Academy of Sciences, vol. 92, no. 15, 1995, pp. 7001–7005., doi:10.1073/pnas.92.15.7001.
[b] Nass, Ralf, et al. “Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults.” Annals of Internal Medicine, vol. 149, no. 9, Apr. 2008, p. 601., doi:10.7326/0003-4819-149-9-200811040-00003.
[c] Svensson, J. “Two-Month Treatment of Obese Subjects with the Oral Growth Hormone (GH) Secretagogue MK-677 Increases GH Secretion, Fat-Free Mass, and Energy Expenditure.” Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 2, Jan. 1998, pp. 362–369., doi:10.1210/jc.83.2.362.
[d] Murphy, M. G., et al. “MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism” The Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 2, 1998, pp. 320–325., doi:10.1210/jcem.83.2.4551.
[e] Chapman, I M, et al. “Stimulation of the Growth Hormone (GH)-Insulin-like Growth Factor I Axis by Daily Oral Administration of a GH Secretogogue (MK-677) in Healthy Elderly Subjects.” The Journal of Clinical Endocrinology & Metabolism, vol. 81, no. 12, 1996, pp. 4249–4257., doi:10.1210/jcem.81.12.8954023.
[f] Copinschi, G. “Effects of a 7-Day Treatment with a Novel, Orally Active, Growth Hormone (GH) Secretagogue, MK-677, on 24-Hour GH Profiles, Insulin-like Growth Factor I, and Adrenocortical Function in Normal Young Men.” Journal of Clinical Endocrinology & Metabolism, vol. 81, no. 8, Jan. 1996, pp. 2776–2782., doi:10.1210/jc.81.8.2776.
[g] Adunsky, Abraham, et al. “MK-0677 (Ibutamoren Mesylate) for the Treatment of Patients Recovering from Hip Fracture: A Multicenter, Randomized, Placebo-Controlled Phase IIb Study.” Archives of Gerontology and Geriatrics, vol. 53, no. 2, 2011, pp. 183–189., doi:10.1016/ j.archger.2010.10.004.
[h] Svensson, J., et al. “Treatment with the Oral Growth Hormone Secretagogue MK-677 Increases Markers of Bone Formation and Bone Resorption in Obese Young Males.” Journal of Bone and Mineral Research, vol. 13, no. 7, Jan. 1998, pp. 1158–1166., doi:10.1359/ jbmr.1998.13.7.1158.
[i] Murphy, M. G., et al. “Effect of Alendronate and MK-677 (a Growth Hormone Secretagogue), Individually and in Combination, on Markers of Bone Turnover and Bone Mineral Density in Postmenopausal Osteoporotic Women.” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 3, 2001, pp. 1116–1125., doi:10.1210/jcem.86.3.7294.
[j] Murphy, M. G., et al. “Oral Administration of the Growth Hormone Secretagogue MK-677 Increases Markers of Bone Turnover in Healthy and Functionally Impaired Elderly Adults.” Journal of Bone and Mineral Research, vol. 14, no. 7, Jan. 1999, pp. 1182–1188., doi:10.1359/ jbmr.1999.14.7.1182.
[k] Chapman, Ian M., et al. “Oral Administration of Growth Hormone (GH) Releasing Peptide- Mimetic MK-677 Stimulates the GH/Insulin-Like Growth Factor-I Axis in Selected GH-Deficient Adults.” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 10, 1997, pp. 3455– 3463., doi:10.1210/jcem.82.10.4297.
[l] Thorner, Michael O., et al. "Growth hormone-releasing hormone and growth hormone- releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging." Recent progress in hormone research 52 (1997): 215-44.
[m] Copinschi, Georges, et al. "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man." Neuroendocrinology 66.4 (1997): 278-286.
[n] Van Cauter, Eve, and Georges Copinschi. "Interrelationships between growthhormone and sleep." Growth Hormone & IGF Research 10 (2000): S57-S62.
[o] Cauter, Eve Van, Laurence Plat, and Georges Copinschi. "Interrelations between sleep and the somatotropic axis." Sleep 21.6 (1998): 553-566.
[p] Steiger, A., et al. "Effects of hormones on sleep." Hormone Research in Paediatrics 49.3-4 (1998): 125-130.
[q] Copinschi, G. E. O. R. G. E. S., et al. "Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men." The Journal of Clinical Endocrinology & Metabolism 81.8 (1996): 2776-2782.
[r] Weikel, Jutta C., et al. "Ghrelin promotes slow-wave sleep in humans." American Journal of Physiology-Endocrinology and Metabolism 284.2 (2003): E407-E415.
[s] McKee, Alexis, and John E. Morley. "Hormones and Sarcopenia." Current Opinion in Endocrine and Metabolic Research (2019).
[t] Schleim, K-D., et al. "Increases in circulating insulin-like growth factor I levels by the oral growth hormone secretagogue MK-0677 in the beagle are dependent upon pituitary mediation." Endocrinology 140.4 (1999): 1552-1558.
[u] Codner, Ethel, et al. "Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone–insulin‐like growth factor I axis in growth hormone–deficient children." Clinical Pharmacology & Therapeutics 70.1 (2001): 91-98.
[v] Akamizu, Takashi, et al. "Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects." European Journal of Endocrinology 150.4 (2004): 447-456.
[w] Schmid, Dagmar A., et al. "Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls." Neuropsychopharmacology 30.6 (2005): 1187-1192.