Mammalian sleep-wake cycle

For some parameter values the model for the mammalian clock fails to allow entrainment by 24-h LD cycles, regardless of the amplitude of the light-induced change in Per expression. The question arises whether there exists a syndrome corresponding to this mode of dynamic behavior predicted by the model. Indeed there exists such a syndrome, known as the non-24-h sleep-wake syndrome, in which the phase of the sleep-wake pattern continuously varies with respect to the LD cycle that is, the patient free-runs in LD conditions [117]. Disorders of the sleep-wake cycle associated with alterations in the dynamics of the circadian clock belong to the broad class of dynamical diseases [122, 123], although the term syndrome seems more appropriate for some of these conditions. 

Circadian clock-controlled rhythms provide most organisms with an orchestrated temporal programme that allows for appropriate timing of physiology (i.e. blood pressure, hormonal levels) and behaviour (i.e. alertness, sleep-wake cycle). The mammalian central circadian pacemaker resides in the suprachiasmatic nucleus (SCN) of the brain (Weaver 1998). At the molecular level, the core oscillator driving the mammahan clock consists of interconnected autoregulatory... 

In general, drug-induced sleep disruption is not regarded as a serious safety risk when considering progression to a phase 1 clinical trial however, for certain indications and patient populations, dmg-induced sleep disruption may be an unacceptable adverse effect. In this context, it is useful to consider the benefit of studying dmg-induced effects on sleep in preclinical models. Given that all mammalian species have measurable sleep/wake cycles, there is the expectation that rodent or non-rodent species used in standard safety assessment studies can serve as... 

Devise a synthesis of melatonin, the mammalian hormone involved in regulating the sleep-wake cycle, from the neurotransmitter serotonin, alcohols, and any needed organic and inorganic reagents. 

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