Prolonged Oral Treatment with MK-677, a Novel Growth Hormone Secretagogue, Improves Sleep Quality in Man

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.

Ghrelin Stimulates Appetite, Imagination of Food, GH, ACTH, and Cortisol, but does not Affect Leptin in Normal Controls

“…Fatigue was the most frequent side effect of ghrelin in our study. In related studies, we (Weikel et al, 2003;Frieboes et al, 1999) and others (Copinschi et al, 1997) reported sleep promotion by ghrelin, GHRP-6, and the GHS MK-677. Interestingly, transient euphoria was found in three subjects.…”

Molecular cloning and mRNA expression analysis of two GH secretagogue receptor transcripts in orange-spotted grouper (Epinephelus coioides)

“…The appearance of gpGhsr mRNA in brain and pituitary is consistent with the main acting sites of ghrelin. Besides stimulating GH secretion (Kojima et al 1999, Riley et al 2002, Kaiya et al 2003a,b, Ran et al 2004, Shepherd et al 2007, ghrelin has also been reported to be involved in other physiological functions controlled by central nervous system, including energy expenditure (Tschop et al 2000), feeding behavior (Nakazato et al 2001, Unniappan et al 2002, Matsuda et al 2006a, Jönsson et al 2007, Miura et al 2007, Shepherd et al 2007, and sleep quality (Copinschi et al 1997). The grouper active receptor form of ghrelin, gpGHSR1a, shows a similar expression pattern as that seen in black seabream .…”

Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine regulation of sleep in humans

“…38 On the other hand, in two studies acute administration of the synthetic peptidyl GHS, MK-0677, modified the sleep pattern in normal subjects. 39,40 In fact, prolonged treatment with oral MK-0677 (25 mg once daily) in elderly subjects increases the length of REM sleep phases, meanwhile decreasing rapid eye movement latency. 41 Hexarelin, another synthetic GHS, exerts similar actions by decreasing stage 4 sleep during the first half of the night and EEG delta power during the entire night.…”