To enhance the chance of immediate entrainment, treatment should commence once the subject begins to slip out of a normal sleep phase, characterized by difficulty initiating sleep (long sleep latency) or difficulty getting up in the morning. In advanced or delayed sleep phase syndrome, melatonin treatment timing should be individually determined based on the extent of their abnormal phase according the melatonin PRC110 and stepwise treatment for particularly advanced or delayed subjects may be warranted.

In all of these disorders, daily Inhibitors,research,lifescience,medical melatonin treatment is a lifelong requirement, as once treatment is stopped, the circadian pacemaker will revert to its endogenous period or phase angle (Figure 6), The safety profile of melatonin, while not assessed for very long-term use in humans, is good,104,120,121 although care should be taken to ensure it is from a reliable source and pharmaceutical grade. In the near future, melatonin analogs will also become approved

for this indication although as with melatonin, a correct initial diagnosis Inhibitors,research,lifescience,medical is required, and precise timing and dose remain to be determined. Acknowledgments The research reported herein was conducted at the University of Surrey and was Inhibitors,research,lifescience,medical NVP-BGJ398 ic50 supported by the South Thames Regional Health Authority, Institut de Recherches Internationale Servier, Stockgrand Ltd., University of Surrey and The Wellcome Trust (Grants 048197/Z/96/Z and Inhibitors,research,lifescience,medical 060018/B/99/Z). SWL is currently supported in part by the US Department of Defense (BC030928), the NIH National Center for Neurological Disorders and Stroke (R01NS040982), and the NIH National Center for Complementary and Alternative Medicine (R01AT002129). DJS is currently supported in part

by grants from EU 6th Framework project EUCLOCK (No. 018741) and EU Marie Curie RTN grant (MCRTN-CT-2004-512362). Selected abbreviations and acronyms 11-OHCS 11-hydroxycorticosteroid aMT6s 6-sulphatoxymelatonin LP light perception NPL no conscious perception of light RHT retinohypothalamic tract SCN suprachiasmatic nuclei
Vigilance states are classified, based on changes Inhibitors,research,lifescience,medical In brain electrical activity as indexed by the electroencephalogram (EEG), into wakefulness, non-rapid CP-673451 supplier eye movement (NREM), and rapid eye movement (REM) sleep. Sleep occurs at specific times in phase with many other circadian variables such as core body temperature and endocrine hormone secretion. Within sleep, REM sleep also follows a circadian rhythm, reaching its maximum duration near body temperature minimum. The recovery process underlying sleep can be indexed by the intensity of NREM sleep as measured by the quantitative EEG within the delta (0.5-4.5 Hz) frequency range. Delta activity is high at sleep onset, in close relation with sleep need and depth, and increases over the baseline level after extended wakefulness. This intensity measure of sleep is relatively independent of the circadian process generated by the suprachiasmatic nuclei (SCN).