MK-677 Oral GH Secretagogue
MK-677 Oral HGH Secretagogue
Info / Links to Studies
Complements from JJB and our other brothers over on AUG!
MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.
AuthorsMurphy MG, et al. Show all Journal
J Clin Endocrinol Metab. 1998 Feb;83(2):320-5.
Abstract
The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24-39 yr) were calorically restricted (18 kcal/kg.day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean +/- SE; MK-677 group -2.67 +/- 0.40 g/day vs. placebo group -2.83 +/- 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 +/- 0.21 g/day in the MK-677 treatment group compared with -1.48 +/- 0.21 g/day in the placebo group (P < 0.01). MK-677 improved nitrogen balance integrated over the 7 days of treatment; area under the curve day 8-14 nitrogen balance response was +2.69 +/- 5.0 (SE) for MK-677 and -8.97 +/- 5.26 g.day for placebo (P < 0.001). MK-677 produced a peak GH response of 55.9 +/- 31.7 micrograms/L after single dose (day 1 of treatment) and 22.6 +/- 9.3 micrograms/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 micrograms/L (treatment day 7). Following the initial 7-day caloric restriction, insulin-like growth factor-I (IGF-I) declined from 232 +/- 25 to 186 +/- 19 ng/mL in the MK-677 group and from 236 +/- 19 to 174 +/- 23 ng/mL in the placebo group. Mean IGF-I concentration increased significantly during MK-677 to 264 +/- 31 ng/mL (mean for the last 5 days of treatment) compared with 188 +/- 19 ng/mL with placebo (P < 0.01). No significant difference in IGF binding protein-2 was found between the MK-677 and placebo treatments. However, the mean in IGF binding protein-3 for the last 5 days of MK-677 treatment was also significantly increased to 3273 +/- 330 ng/mL (mean +/- SE) compared with placebo 2604 +/- 253 ng/mL (P < 0.01). Neither the serum cortisol nor the PRL response was significantly greater after 7 days of MK-677 dosing compared with 7 days of placebo. MK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences. In conclusion, MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.
Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.
AuthorsCopinschi G, et al. Show all Journal
Neuroendocrinology. 1997 Oct;66(4):278-86.
Affiliation
Abstract
Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.
LINKS TO SOME STUDIES AND SOME MK677 RESEARCH
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9467534
Summary of Study: Raises serum IGF-1/IGFBP-3, able to REVERSE diet induced nitrogen wasting (protein catabolism due to calorie restriction).
Done on HEALTHY volunteers.
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9349662
Summary of Study: Sleep patterns were less interrupted, REM and deep sleep was significantly increased. Done on HEALTHY volunteers of age 18-30. Effect was seen much greater in elderly subjects.
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=8768828
Summary of Study: 7 day study on GH/IGF-1 effects after once daily administration. Showed similar GH release in all three concentrations (placebo/5mg/25mg) but dose dependant increases in serum IGF-1 in 5mg/25mg. Also showed an increase in GH pulses. Done on 9 HEALTHY young males.
Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue
This text shows the full chemical structure of MK0677 as well as how to synthesize it, available also in PDF. (It is referred to as L-163,191). Shows btw that oral availability is >60% and that it can form solution with water greater than 100mg/ml.
N-[1(R)-[(1,2-dihydro-1-methanesulfonylspiro[3H-indole-3,4'-piperidin]-1'-y l)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide methanesulfonate is MK-0677
http://patft.uspto.gov/netacgi/nph-P...y=PN/5773441
Patent information regarding ibutamoren mesylate.
MK-677 Oral HGH Secretagogue
Info / Links to Studies
Complements from JJB and our other brothers over on AUG!
MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.
AuthorsMurphy MG, et al. Show all Journal
J Clin Endocrinol Metab. 1998 Feb;83(2):320-5.
Abstract
The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24-39 yr) were calorically restricted (18 kcal/kg.day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean +/- SE; MK-677 group -2.67 +/- 0.40 g/day vs. placebo group -2.83 +/- 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 +/- 0.21 g/day in the MK-677 treatment group compared with -1.48 +/- 0.21 g/day in the placebo group (P < 0.01). MK-677 improved nitrogen balance integrated over the 7 days of treatment; area under the curve day 8-14 nitrogen balance response was +2.69 +/- 5.0 (SE) for MK-677 and -8.97 +/- 5.26 g.day for placebo (P < 0.001). MK-677 produced a peak GH response of 55.9 +/- 31.7 micrograms/L after single dose (day 1 of treatment) and 22.6 +/- 9.3 micrograms/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 micrograms/L (treatment day 7). Following the initial 7-day caloric restriction, insulin-like growth factor-I (IGF-I) declined from 232 +/- 25 to 186 +/- 19 ng/mL in the MK-677 group and from 236 +/- 19 to 174 +/- 23 ng/mL in the placebo group. Mean IGF-I concentration increased significantly during MK-677 to 264 +/- 31 ng/mL (mean for the last 5 days of treatment) compared with 188 +/- 19 ng/mL with placebo (P < 0.01). No significant difference in IGF binding protein-2 was found between the MK-677 and placebo treatments. However, the mean in IGF binding protein-3 for the last 5 days of MK-677 treatment was also significantly increased to 3273 +/- 330 ng/mL (mean +/- SE) compared with placebo 2604 +/- 253 ng/mL (P < 0.01). Neither the serum cortisol nor the PRL response was significantly greater after 7 days of MK-677 dosing compared with 7 days of placebo. MK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences. In conclusion, MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.
Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.
AuthorsCopinschi G, et al. Show all Journal
Neuroendocrinology. 1997 Oct;66(4):278-86.
Affiliation
Abstract
Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.
LINKS TO SOME STUDIES AND SOME MK677 RESEARCH
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9467534
Summary of Study: Raises serum IGF-1/IGFBP-3, able to REVERSE diet induced nitrogen wasting (protein catabolism due to calorie restriction).
Done on HEALTHY volunteers.
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9349662
Summary of Study: Sleep patterns were less interrupted, REM and deep sleep was significantly increased. Done on HEALTHY volunteers of age 18-30. Effect was seen much greater in elderly subjects.
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=8768828
Summary of Study: 7 day study on GH/IGF-1 effects after once daily administration. Showed similar GH release in all three concentrations (placebo/5mg/25mg) but dose dependant increases in serum IGF-1 in 5mg/25mg. Also showed an increase in GH pulses. Done on 9 HEALTHY young males.
Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue
This text shows the full chemical structure of MK0677 as well as how to synthesize it, available also in PDF. (It is referred to as L-163,191). Shows btw that oral availability is >60% and that it can form solution with water greater than 100mg/ml.
N-[1(R)-[(1,2-dihydro-1-methanesulfonylspiro[3H-indole-3,4'-piperidin]-1'-y l)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide methanesulfonate is MK-0677
http://patft.uspto.gov/netacgi/nph-P...y=PN/5773441
Patent information regarding ibutamoren mesylate.
