Effects of the melatonin MT-1/MT-2 agonist ramelteon on daytime body temperature and sleep.
OBJECTIVE
A reduction in core temperature and an increase in the distal-proximal skin gradient (DPG) are reported to be associated with shorter sleep onset latencies (SOL) and better sleep quality. Ramelteon is a melatonin MT-1/MT-2 agonist approved for the treatment of insomnia. At night, ramelteon has been reported to shorten SOL. In the present study we tested the hypothesis that ramelteon would reduce core temperature, increase the DPG, as well as shorten SOL, reduce wakefulness after sleep onset (WASO), and increase total sleep time (TST) during a daytime sleep opportunity.


METHODS
Randomized, double-blind, placebo-controlled, cross-over design. Eight mg ramelteon or placebo was administered 2 h prior to a 4-h daytime sleep opportunity.


METHODS
Sleep and chronobiology laboratory.


METHODS
Fourteen healthy adults (5 females), aged (23.2 +/- 4.2 y).


RESULTS
Primary outcome measures included core body temperature, the DPG and sleep physiology (minutes of total sleep time [TST], wake after sleep onset [WASO], and SOL). We also assessed as secondary outcomes, proximal and distal skin temperatures, sleep staging and subjective TST. Repeated measures ANOVA revealed ramelteon significantly reduced core temperature and increased the DPG (both P < 0.05). Furthermore, ramelteon reduced WASO and increased TST, and stages 1 and 2 sleep (all P < 0.05). The change in the DPG was negatively correlated with SOL in the ramelteon condition.


CONCLUSIONS
Ramelteon improved daytime sleep, perhaps mechanistically in part by reducing core temperature and modulating skin temperature. These findings suggest that ramelteon may have promise for the treatment of insomnia associated with circadian misalignment due to circadian sleep disorders.
Markwald
Rachel R
RR
Department of Integrative Physiology, Sleep and Chronobiology Laboratory, Center for Neuroscience, University of Colorado, Boulder, CO 80309-0354, USA.
Lee-Chiong
Teofilo L
TL
Burke
Tina M
TM
Snider
Jesse A
JA
Wright
Kenneth P
KP
D000328:Adult; D000704:Analysis of Variance; D001831:Body Temperature / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects*; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
D007192:Indenes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C495910:ramelteon