The Use of Chronobiotics in the Resynchronization of the Sleep–wake Cycle

Abstract

Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new type of agents called 'chronobiotics', among which melatonin is the prototype. The term 'chronobiotic' defines as a substance capable of shifting the phase of the circadian time system thus re-entraining circadian rhythms. Melatonin administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome or jet lag, as well in shift-workers. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect). We successfully employed the timely use of three factors (melatonin treatment, exposure to light, physical exercise) to hasten the resynchronization after transmeridian flights comprising 12-13 time zones, from an average of 8-10 days to about 2 days. Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer's dementia patients. About 45% of dementia patients have severe disruptions in their sleep-wakefulness cycle. Both in aged subjects having very minimal sleep disorders as well as in demented patients with a very severe disorganization of the sleep-wake cycle, melatonin treatment reduced the variability of sleep onset and restored sleep.

24-Hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect of melatonin or α-ketoglutarate

“…substances capable of shifting the phase of the circadian time system; therefore, it can act by re-entraining circadian rhythmicity. 8,9 This activity can be relevant if circadian periodicity is taken as an index of host and tumor cell proliferation and for response to cancer treatments. 5 In patients with metastatic colorectal cancer, severe alterations of the rest-activity circadian rhythm predicted for Table 3 are shown. a 5-fold increase in the risk of death as compared to a normal rest-activity pattern.…”

“…5 NDEA generally delayed acrophases of 24-h rhythms in circulating lipid peroxides and antioxidants, an effect partially counteracted by the co-administration of α-KG. 7 In view of the significant activity that melatonin has on the circadian system, 8,9 we considered it worthwhile to compare the effects of melatonin and α-KG on 24-h rhythmicity in antioxidant defenses in NDEA-injected rats.…”

Melatonin and the Metabolic Syndrome: Physiopathologic and Therapeutical Implications

“…In addition, at pharmacological doses, presumably via antioxidant and anti-inflammatory effects, melatonin inhibits tumor growth. As the prototype of the chronobiotic class of drugs [19,20,21], melatonin restores the phase and amplitude of circadian rhythmicity by interaction with MT 1 and MT 2 melatonin receptors expressed in the hypothalamic SCN and other brain regions.…”

Timing of Activities and their Effects on Circadian Rhythm in the Elderly with Dementia: A Literature Review

“…Thus, engaging in activities at times when biological circadian processes are conducive to the specific activity can create optimal efficiency and output [31]. As aging occurs, circadian rhythms begin to become asynchronous.…”