Melatonin (N-acetyl-5-methoxytryptamine) is a hormone which is synthesized and secreted primarily by the pineal gland. The pineal body, situated in the epithalamus at the centre of the brain, synthesises and releases melatonin into the general circulation only during nocturnal darkness, irrespective of whether a species is nocturnal or diurnal in its behavioural activity pattern. The pineal gland is recognized as a neuroendocrine transducer, whose chief function is that of synchronizing endogenous circadian rhythms via the conversion of neuronal impulses to melatonin release. Aging is characterized by disorganization of circadian rhythms caused in part by the progressive decline in the activity of the pineal gland leading ultimately to pineal failure. The production of melatonin is induced by the perception of darkness as transmitted from the eyes to the pineal gland between the two hemispheres of the brain. The pineal gland of a normal person produces approximately 500 mcg of melatonin daily. Being lipid soluble, melatonin rapidly crosses the blood brain barrier and other tissues. Once released from the pineal gland, which is highly vascularized, melatonin enters the general circulation and the cerebrospinal fluid (CSF).
Melatonin acts on the central and peripheral nervous system as well as on peripheral endocrine target tissues and has been implicated in many human disorders. Some disorders are known to be linked to chronobiologic abnormalities. Melatonin release appears to be robust and resistant to change by a variety of potent stimuli. The stability of the melatonin rhythm makes melatonin an ideal candidate as a biological timing hormone, a role which is indisputable for rhythms in photo-sensitive seasonal breeding mammals and has been postulated for daily rhythms in non-seasonal breeders. The synthesis and secretion of melatonin shows a significant circadian rhythm and its production decreases with age. The highest levels of melatonin are found in children age 5 and under, after which levels begin to decline.
The pineal hormone melatonin has several putative functions, including regulation of circadian rhythms, regulation of the reproductive axis and antioxidant activity. Melatonin influences circadian rhythm and mediates the effects of photoperiod on reproductive function in seasonally breeding mammals. In humans, melatonin administration has been shown to alleviate the symptoms of jet lag after air travel across several time zones. The hormone also has potent sedative effects in humans and may be a useful hypnotic agent. Melatonin is involved in the transduction of photoperiodic information and appears to modulate a variety of neural and endocrine functions in vertebrates, including the regulation of reproduction, body weight and metabolism in photoperiodic mammals, the control of circadian rhythms and the modulation of retinal physiology. Melatonin participates in several important physiological functions including the control of seasonal reproduction, improving immunological function, promoting sleeping, cancer inhibition and anti-aging. Recently, it was found that melatonin is a potent endogenous free radical scavenger. Melatonin production has been shown to change across the lifespan, peaking in childhood and gradually decreasing after puberty. The gradual decline in the secretory activity of the pineal gland after puberty has been linked with the process of aging as melatonin is thought to counteract the deleterious effects of oxygen free radicals - unstable molecules thought to play an important part in atherosclerosis and other diseases associated with aging. Melatonin is involved in the regulation of circadian rhythms and a variety of neural and endocrine functions. It is now well established that the hormone melatonin plays a crucial role in the maintenance of circadian rhythms. The cycle of melatonin production and the cessation of production therefore underlie the circadian rhythm. Melatonin has been implicated in a number of human disorders, particularly those relating to chronobiologic abnormalities.
Melatonin is involved in the transduction of photoperiodic information and appears to modulate a variety of neural and endocrine functions in vertebrates, including the regulation of reproduction, body weight and metabolism in photoperiodic mammals, control of circadian rhythms, and modulation of retinal physiology. Impaired pineal melatonin function has been implicated in the pathophysiology of numerous systemic, neurological and mental disorders including cancer, autoimmune disorders, AIDS, diabetes mellitus, hyper-cholesterolemia, mental depression including seasonal affective disorder (SAD), schizophrenia, autism, panic disorder, obsessive compulsive disorder, trichotillomania, impulsive and aggressive behavior, chronic insomnia, sleep paralysis, bulimia, Parkinson's disease, Huntington's chorea, AIDS dementia, Alzheimer's disease, chronic pain syndromes, diabetic neuropathy, epilepsy, narcolepsy, migraine, multiple sclerosis, ischemic stroke, motor neuron disease, traumatic spinal cord injuries and macular degeneration. These diseases are associated either with deficient melatonin production and/or disruption of melatonin circodian rhythmicity associated with deficient or dysregulated serotonin neurotransmission. Exogenous administration of melatonin has been found by several investigators to facilitate sleep onset and improve quality of sleep. Exogenous melatonin administration has been used to treat jet-lag related sleep disturbances, considered to be caused by desynchronization of circadian rhythms. Melatonin is usually administered orally but it takes over an hour after administration for the blood plasma concentration of the active agent to reach its peak. Other routes of administration, in particular nasal administration have been considered. However, because of inherent problems, inter alia due to the low solubility of melatonin in water, melatonin compositions suitable for nasal administration have yet to be prepared. |
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