Abstract：
:Several novel melatonin receptor agonists, in addition to various formulations of melatonin itself, are either available or in development for the treatment of insomnia. Melatonin is thought to exert its effects principally through two high affinity, G-protein coupled receptors, MT1 and MT2, though it is not known which subtype is responsible for the sleep-promoting action. The present study used radiotelemetry to record EEG and EMG in un-restrained freely moving rats to monitor the sleep-wake behaviour and examined the acute sleep-promoting activity of an MT2 receptor subtype selective melatonin analog, IIK7. IIK7 is a full agonist at the MT2 receptor subtype but a partial agonist at the MT1 receptor and has approximately 90-fold higher affinity for MT2 than MT1. Like melatonin, IIK7 (10mg/kg i.p.) significantly reduced NREM sleep onset latency and transiently increased the time spent in NREM sleep, but did not alter REM sleep latency or the amount of REM sleep. An analysis of the EEG power spectrum showed no change in delta (1-4 Hz) or theta activity (5-8 Hz) following IIK7 administration. Core body temperature was slightly decreased ( approximately 0.3 degrees C) by IIK7 compared to vehicle-treated rats. The acute and transient changes in the sleep-wake cycle mimic the changes seen with melatonin and suggest that its sleep-promoting activity is mediated by activation of the MT2 receptor subtype.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Fisher SP,Sugden Ddoi
10.1016/j.neulet.2009.04.005subject
Has Abstractpub_date
2009-06-26 00:00:00pages
93-6issue
2eissn
0304-3940issn
1872-7972pii
S0304-3940(09)00455-8journal_volume
457pub_type
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