This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hirai, K. Articles by Miyamoto, M. Search for Related Content PubMed PubMed Citation Articles by Hirai, K. Articles by Miyamoto, M. Social Bookmarking                         What's this?

Ramelteon (TAK-375) Accelerates Reentrainment of Circadian Rhythm after a Phase Advance of the Light-Dark Cycle in Rats

Muneto Kita

Hiroyuki Ohta

Hisao Nishikawa

Yuu Fujiwara

Pharmacology Research Laboratories I, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Osaka, Japan

Shigenori Ohkawa

Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Osaka, Japan

Masaomi Miyamoto

Pharmacology Research Laboratories I, Pharmaceutical Research Division; Strategic Product Planning Department, Takeda Pharmaceutical Company Ltd., 4-1-1, Doshomachi, Chuo-ku, Osaka 540-8645, Japan;Miyamoto_Masaomi{at}takeda.co.jp

In vivo pharmacological effects of ramelteon (TAK-375), a novel, highly MT1/MT2-selective receptor agonist, were studied in rats to determine ramelteon’s ability to reentrain the circadian rhythm after an abrupt phase advance. Experiments were also conducted to assess the potential cognitive side effects of ramelteon and its potential to become a drug of abuse. After an abrupt 8-h phase shift, ramelteon (0.1 and 1 mg/kg, p.o.) and melatonin (10 mg/kg, p.o.) accelerated reentrainment of running wheel activity rhythm to the new lightdark cycle. Ramelteon (3-30 mg/kg, p.o.) and melatonin (10-100 mg/kg, p.o.) did not affect learning or memory in rats tested by the water maze task and the delayed match to position task, although diazepam and triazolam impaired both of the tasks. Neither ramelteon (3-30 mg/kg, p.o.) nor melatonin (10-100mg/kg, p.o.) demonstrated a rewarding property in the conditioned place-preference test, implying that MT₁/MT₂ receptor agonists have no abuse potential. In contrast, benzodiazepines and morphine showed rewarding properties in this test. The authors’ results suggest that ramelteon may be useful for treatment of circadian rhythm sleep disorders without adverse effects typically associated with benzodiazepine use, such as learning and memory impairment, and drug dependence.

Key Words: ramelteon (TAK-375) • circadian rhythms • phase shift • reentrainment • learning and memory • place preference • dependence • benzodiazepines

Journal of Biological Rhythms, Vol. 20, No. 1, 27-37 (2005)
DOI: 10.1177/0748730404269890


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B. J. Prendergast MT1 Melatonin Receptors Mediate Somatic, Behavioral, and Reproductive Neuroendocrine Responses to Photoperiod and Melatonin in Siberian Hamsters (Phodopus sungorus) Endocrinology, February 1, 2010; 151(2): 714 - 721. [Abstract] [Full Text] [PDF]

				J. Arendt and S. M. W. Rajaratnam Melatonin and its agonists: an update The British Journal of Psychiatry, October 1, 2008; 193(4): 267 - 269. [Abstract] [Full Text] [PDF]

				P. V. Agostino, S. A. Plano, and D. A. Golombek Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules PNAS, June 5, 2007; 104(23): 9834 - 9839. [Abstract] [Full Text] [PDF]