Acute effects of melatonin and its time of administration on core body temperature and heart rate in cynomolgus monkeys.
We examined the effects of exogenous melatonin and the time of its administration on core body temperature (CBT) and heart rate (HR) in cynomolgus monkeys. Doses of melatonin at 0.2, 2, 20 and 200 mg/kg were administered by oral gavage once daily at different times. With administration at 09.00 h, melatonin dose-dependently suppressed CBT and the effect reached statistical significance at 200 mg/kg. With administration at 16.00 h, the suppressive effect on CBT was not evident for several hours after administration possibly due to masking by the normal robust CBT decline. Unexpectedly, melatonin inhibited the normal CBT decline thereafter and this resulted in an upward shift of the CBT nadir during the dark phase especially with 200 mg/kg. The HR showed a similar upward shift at that time. Any effects on the CBT and HR from melatonin administration were not inhibited by luzindole, an MT(1)/MT(2) receptor antagonist, whereas N-acetyl-5-hydroxytryptamine, a ligand of the MT(3) binding site, mimicked all the actions of melatonin. To our knowledge, this is the first time it has been shown that melatonin administered in the early evening promotes upward shifting of the CBT and HR in the nighttime in addition to the daytime decrease in the CBT. These changes may be mediated, at least partly, through the MT(3) binding site.
Inui
Yoshitaka
Y
Development Research Center, Takeda Pharmaceutical Company Limited, Jusohonmachi 2-chome, Yodogawa-ku, Osaka, Japan. Inui_Yoshitaka@takeda.co.jp
Hazeki
Osamu
O
D000818:Animals; D001665:Binding Sites; D001683:Biological Clocks / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000378:metabolism
D044094:Receptors, Melatonin; D008550:Melatonin