The circadian rhythm of pineal
melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle.
Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (
melatonin 1a) and MT(2) (
melatonin 1b) receptors, the two major
melatonin receptor subtypes found in mammals. Both receptors are highly concentrated in the SCN. In diurnal animals, exogenous
melatonin induces sleep over a wide range of doses. In healthy humans,
melatonin also induces sleep, although its maximum
hypnotic effectiveness, as shown by studies of the timing of dose administration, is influenced by the circadian phase. In both young and elderly individuals with
primary insomnia, nocturnal plasma
melatonin levels tend to be lower than those in healthy controls. There are data indicating that, in affected individuals,
melatonin therapy may be beneficial for ameliorating
insomnia symptoms.
Melatonin has been successfully used to treat
insomnia in children with
attention-deficit hyperactivity disorder or
autism, as well as in other
neurodevelopmental disorders in which sleep disturbance is commonly reported. In
circadian rhythm sleep disorders, such as
delayed sleep-phase syndrome,
melatonin can significantly advance the phase of the sleep/wake rhythm. Similarly, among shift workers or individuals experiencing
jet lag,
melatonin is beneficial for promoting adjustment to work schedules and improving sleep quality. The
hypnotic and rhythm-regulating properties of
melatonin and its agonists (
ramelteon,
agomelatine) make them an important addition to the armamentarium of drugs for treating primary and
secondary insomnia and
circadian rhythm sleep disorders.