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Increasing plasma melatonin concentrations are associated with increased sleepiness. Suppression of melatonin production correlates with insomnia. The MT2 receptor, found in the hypothalamic suprachiasmatic nucleus and the neural retina, is thought to mediate the effects of melatonin on circadian rhythms and regulate visual function.The role of the MT3 receptor has not been defined.9 Endogenous melatonin secretion occurs approximately two hours before an individual’s habitual bedtime and is correlated with the onset of evening sleepiness. Melatonin is a neurohormone released from the pineal gland in association with the light–dark cycle that regulates sleep.The sleep-promoting and circadian effects of melatonin are attributed to interactions with two subtypes of human melatonin receptors:MT1 and MT2.7 A third subtype,MT3, is a peripheral receptor.8The MT1 receptor, localized in the hypothalamic suprachiasmatic nucleus, is believed to mediate circadian and reproductive effects of melatonin. 1 In the 2005 Sleep in America Poll, 7% of respondents reported using prescription sleep medication at least a few nights each month, 9% reported using over-the-counter sleep aids, 11% reported using alcohol, beer or wine specifically to help them sleep, and 2% reported using melatonin for sleep. 1,2 Limited data also suggest that melatonin is effective in the treatment of chronic insomnia. 6 Antidepressants and antihistamines are also effective in some patients, but have troublesome adverse effects. 2,5 Although highly effective at reducing sleep latency, benzodiazepine and the nonbenzodiazepine benzodiazepine receptor agonists are associated with varying degrees of residual daytime sedation, abuse liability, and toxicity. 2 Pharmacological agents include benzodiazepines, non-benzodiazepine benzodiazepine receptor agonists, antihistamines, antidepressants, melatonin, herbal products, and nutritional supplements. Management of insomnia includes sleep hygiene education, cognitive behavioral therapy, and pharmacological therapy. Up to 75% of adults report symptoms of a sleep problem occurring a few nights per week or more, while approximately 10–15% have chronic insomnia. 1,2 Acute insomnia refers to periods of difficulty sleeping lasting one day to a few weeks, while chronic insomnia refers to sleep difficulty lasting at least three nights per week for one month or more. Insomnia can result in daytime consequences, including tiredness, difficulty concentrating, and irritability, as well as increased healthcare utilization and reduced work productivity, lower quality of life or quality of social relationships, and decrements in memory, mood, or cognitive function. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.Insomnia is a common condition characterized by difficulty falling asleep, increased night-time wakefulness or inadequate sleep duration.
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Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects.
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Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals.