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Ibutamoren

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Ibutamoren
Clinical data
Other namesMK-677; MK-0677; L-163,191; Oratrope
Routes of
administration		By mouth
Legal status
Legal status
Pharmacokinetic data
Elimination half-life4–6 hours (in beagles);[1] IGF-1 levels remain elevated in humans with a single oral dose for up to 24 hours[2]
Identifiers
  • 2-amino-2-methyl-N-[1-(1-methylsulfonylspiro[2H-indole-3,4'-piperidine]-1'-yl)-1-oxo-3-phenylmethoxypropan-2-yl]propanamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.236.734 Edit this at Wikidata
Chemical and physical data
FormulaC27H36N4O5S
Molar mass528.67 g·mol−1
3D model (JSmol)
  • O=S(C)(=O)N(C2)c1ccccc1C23CCN(CC3)C(=O)C(NC(=O)C(N)(C)C)COCc4ccccc4
  • InChI=1S/C27H36N4O5S/c1-26(2,28)25(33)29-22(18-36-17-20-9-5-4-6-10-20)24(32)30-15-13-27(14-16-30)19-31(37(3,34)35)23-12-8-7-11-21(23)27/h4-12,22H,13-19,28H2,1-3H3,(H,29,33)/t22-/m1/s1
  • Key:UMUPQWIGCOZEOY-JOCHJYFZSA-N
  (verify)

Ibutamoren (INNTooltip International Nonproprietary Name) (developmental code names MK-677, MK-0677, LUM-201, L-163,191; former tentative brand name Oratrope) is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin.[3][4][5][6][7] It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.[8]

Effect on lean mass

Ibutamoren has been shown to sustain activation of the GH–IGF-1 axis and to increase lean body mass with no change in total fat mass or visceral fat. It is under investigation as a potential treatment for reduced levels of these hormones, such as in children or elderly adults with growth hormone deficiency,[3][9][10][11] and human studies have shown it to increase both muscle mass and bone mineral density,[12][13] making it a promising potential therapy for the treatment of frailty in the elderly.[14][15] As of June 2017, ibutamoren is in the preclinical stage of development for growth hormone deficiency.[3]

Effect on sleep architecture

In a small study of 14 subjects, MK-677 dosed at 25mg/day at bedtime was shown to increase REM sleep by 20% and 50% in young and older subjects respectively.[16] Treatment with MK-677 also resulted in an approximate 50% increase in stage IV sleep in young subjects.[16]

Non-research use

Since MK-677 is still an Investigational New Drug, it has not yet been approved to be marketed for consumption by humans in the United States.[3] However, it has been used experimentally by some in the bodybuilding community. Since it chemically mimics the hormone ghrelin, it functions as a neuropeptide in the central nervous system and crosses the blood-brain-barrier.[4][5][6][7] According to some recent research and discussion, there is a concern that its particularly longer half-life might over-stimulate the ghrelin receptors in the brain.[17]

See also

References

  1. ^ Smith RG, Thorner MO (28 January 2000). Human Growth Hormone: Research and Clinical Practice. Springer Science & Business Media. pp. 45–. ISBN 978-1-59259-015-5.
  2. ^ Smith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, et al. (October 1997). "Peptidomimetic regulation of growth hormone secretion". Endocrine Reviews. 18 (5). The Endocrine Society: 621–645. doi:10.1210/edrv.18.5.0316. PMID 9331545.
  3. ^ a b c d "Ibutamoren - Lumos Pharma/Merck". AdisInsight.
  4. ^ a b Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G (July 1995). "Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue". Proceedings of the National Academy of Sciences of the United States of America. 92 (15): 7001–5. Bibcode:1995PNAS...92.7001P. doi:10.1073/pnas.92.15.7001. PMC 41459. PMID 7624358.
  5. ^ a b Pong SS, Chaung LY, Dean DC, Nargund RP, Patchett AA, Smith RG (January 1996). "Identification of a new G-protein-linked receptor for growth hormone secretagogues". Molecular Endocrinology. 10 (1): 57–61. doi:10.1210/mend.10.1.8838145. PMID 8838145.
  6. ^ a b Cassoni P, Papotti M, Ghè C, Catapano F, Sapino A, Graziani A, Deghenghi R, Reissmann T, Ghigo E, Muccioli G (April 2001). "Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines". The Journal of Clinical Endocrinology and Metabolism. 86 (4): 1738–45. doi:10.1210/jcem.86.4.7402. PMID 11297611.
  7. ^ a b Holst B, Frimurer TM, Mokrosinski J, Halkjaer T, Cullberg KB, Underwood CR, Schwartz TW (January 2009). "Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor". Molecular Pharmacology. 75 (1): 44–59. doi:10.1124/mol.108.049189. PMID 18923064. S2CID 2218638.
  8. ^ Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, Mendel CM, Caufriez A, Leproult R, Bolognese JA, De Smet M, Thorner MO, Van Cauter E (August 1996). "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 and Metabolism. 81 (8): 2776–82. doi:10.1210/jcem.81.8.8768828. PMID 8768828.
  9. ^ Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, et al. (December 1996). "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 and Metabolism. 81 (12): 4249–57. doi:10.1210/jcem.81.12.8954023. PMID 8954023.
  10. ^ Thorner MO, Chapman IM, Gaylinn BD, Pezzoli SS, Hartman ML (1997). "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: 215–44, discussion 244–6. PMID 9238854.
  11. ^ Chapman IM, Pescovitz OH, Murphy G, Treep T, Cerchio KA, Krupa D, Gertz B, Polvino WJ, Skiles EH, Pezzoli SS, Thorner MO (October 1997). "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 and Metabolism. 82 (10): 3455–63. doi:10.1210/jcem.82.10.4297. PMID 9329386.
  12. ^ Murphy MG, Bach MA, Plotkin D, Bolognese J, Ng J, Krupa D, Cerchio K, Gertz BJ (July 1999). "Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group". Journal of Bone and Mineral Research. 14 (7): 1182–8. doi:10.1359/jbmr.1999.14.7.1182. PMID 10404019.
  13. ^ Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ (March 2001). "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 and Metabolism. 86 (3): 1116–25. doi:10.1210/jcem.86.3.7294. PMID 11238495.
  14. ^ Smith RG, Sun Y, Jiang H, Albarran-Zeckler R, Timchenko N (November 2007). "Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging". Annals of the New York Academy of Sciences. 1119 (1): 147–64. Bibcode:2007NYASA1119..147S. doi:10.1196/annals.1404.023. PMID 18056963. S2CID 3220799.
  15. ^ "An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults". ScienceDaily. 5 November 2008.
  16. ^ a b Copinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, et al. (October 1997). "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man". Neuroendocrinology. 66 (4): 278–286. doi:10.1159/000127249. PMID 9349662.
  17. ^ Meyer RM, Burgos-Robles A, Liu E, Correia SS, Goosens KA (December 2014). "A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear". Molecular Psychiatry. 19 (12): 1284–94. doi:10.1038/mp.2013.135. PMC 3988273. PMID 24126924.
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