Ibutamoren

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Ibutamoren
From Wikipedia, the free encyclopedia


Investigational New Drug


Ibutamoren (INN) (developmental code names MK-677, MK-0677, 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]

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]

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 .[16]

[liftsiron]

Clin Pharmacol Ther

. 2001 Jul;70(1):91-8.
doi: 10.1067/mcp.2001.116514.
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
E Codner 1 , F Cassorla, A N Tiulpakov, M V Mericq, A Avila, O H Pescovitz, J Svensson, K Cerchio, D Krupa, B J Gertz, G Murphy
Affiliations

PMID: 11452249 DOI: 10.1067/mcp.2001.116514

Abstract

Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH) secretagogue, stimulates GH release through a pituitary and hypothalamic receptor that is different from the GH-releasing hormone receptor. We evaluated the safety and tolerability and the GH-insulin-like growth factor (IGF) responses to two dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to 8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height < 10th percentile for age, and a maximum GH response of < or = 10 microg/L to two different GH stimulation tests. The children were assigned as follows to one of three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day 15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in groups I and II were studied first to assess safety at the low dose before advancement to the high dose. Hormonal profiles were evaluated on day -1 (baseline) and day 15, and the results were expressed as the change from baseline within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8 days (group III), the median increases (on day 15) from baseline were as follows: 3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3 microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to 116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum cortisol, and insulin concentrations or 24-hour urinary free cortisol after administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We conclude that short-term administration of ibutamoren mesylate can increase GH, IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound is applicable for testing its effect on growth velocity.

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J Clin Endocrinol Metab

. 1996 Aug;81(8):2776-82.
doi: 10.1210/jcem.81.8.8768828.
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
G Copinschi 1 , A Van Onderbergen, M L'Hermite-Balériaux, C M Mendel, A Caufriez, R Leproult, J A Bolognese, M De Smet, M O Thorner, E Van Cauter
Affiliations

PMID: 8768828 DOI: 10.1210/jcem.81.8.8768828

Abstract

To assess the effects of prolonged administration of a novel analog of GH-releasing peptide (MK-677), nine healthy young men participated in a randomized, double blind, three-period cross-over comparison of orally administered placebo and 5- and 25-mg doses of MK-677. Each period involved bedtime administration of the drug for 7 consecutive days. At the end of each period, plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured at 0745 h, and 24-h profiles of plasma GH and cortisol were obtained at 15-min intervals together with the 24-h urinary excretion of free cortisol. Profiles of plasma free cortisol were calculated at hourly intervals. The amounts of GH secreted were similar in all three conditions, but GH pulse frequency was increased with both dosages of the drug, primarily because of an increase in the number of low amplitude pulses. Plasma IGF-I levels were increased in a dose-dependent manner, whereas IGFBP-3 levels were increased only with the highest dosage. There was a positive relationship between GH pulse frequency and IGF-I increase. Except for an advance in the nocturnal nadir and in the morning elevation, MK-677 had no effect on cortisol profiles. In particular, 24-h mean levels of plasma total and free cortisol and urinary excretion of free cortisol were similar under all conditions. The present data suggest that the use of MK-677 for the treatment of relative somatotropic deficiency, particularly in older adults compromised by such deficiency, deserves further investigation.

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J Clin Endocrinol Metab

. 1996 Dec;81(12):4249-57.
doi: 10.1210/jcem.81.12.8954023.
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
I M Chapman 1 , M A Bach, E Van Cauter, M Farmer, D Krupa, A M Taylor, L M Schilling, K Y Cole, E H Skiles, S S Pezzoli, M L Hartman, J D Veldhuis, G J Gormley, M O Thorner
Affiliations

PMID: 8954023 DOI: 10.1210/jcem.81.12.8954023

Abstract

Aging is associated with declining activity of the GH axis, possibly contributing to adverse body composition changes and increased incidence of cardiovascular disease. The stimulatory effects on the GH-insulin-like growth factor I (IGF-I) axis of orally administered MK-677, a GH-releasing peptide mimetic, were investigated. Thirty-two healthy subjects (15 women and 17 men, aged 64-81 yr) were enrolled in a randomized, double blind, placebo-controlled trial. They received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. At baseline and on day 14 of each study period, blood was collected every 20 min for 24 h to measure GH, PRL, and cortisol. Attributes of pulsatile GH release were assessed by 3 independent algorithms. MK-677 administration for 2 weeks increased GH concentrations in a dose-dependent manner, with 25 mg/day increasing mean 24-h GH concentration 97 +/- 23% (mean +/- SE; P < 0.05 vs. baseline). This increase was due to an enhancement of preexisting pulsatile GH secretion. GH pulse height and interpulse nadir concentrations increased significantly without significant changes in the number of pulses. With 25 mg/day MK-677 treatment, mean serum IGF-I concentrations increased into the normal range for young adults (141 +/- 21 microgram/L at baseline, 219 +/- 21 micrograms/L at 2 weeks, and 265 +/- 29 micrograms/L at 4 weeks; P < 0.05). MK-677 produced significant increases in fasting glucose (5.4 +/- 0.3 to 6.8 +/- 0.4 mmol/L at 4 weeks; P < 0.01 vs. baseline) and IGF-binding protein-3. Circulating cortisol concentrations did not change, and PRL concentrations increased 23%, but remained within the normal range. Once daily treatment of older people with oral MK-677 for up to 4 weeks enhanced pulsatile GH release, significantly increased serum GH and IGF-I concentrations, and, at a dose of 25 mg/day, restored serum IGF-I concentrations to those of young adults.

[Puff88]

Thanks for the read. Been thinking about giving mk 677 a try.