Melatonin is a bioprecursor of hypnotic acetyl metabolites produced by the enzymatic acetylation of both melatonin and 2-oxomelatonin under the control of serotonin N-acetyltransferases (NATs) found in the pineal gland, according to pharmacokinetic studies in young and elderly human volunteers and measurements of hypnotic effects in chicks under alternate light-dark or Melatonin’s acetyl metabolite, known as carbo2, is a N-acetyl—carboline. The electroencephalograph (EEG) architecture of this compound’s sleep is comparable to that of physiological sleep, with a high amount of slow-wave deep sleep and rapid eye movement sleep. This contrasts sharply with the EEG sleep architecture reported with GABAergic (-aminobutyric acid) drugs. Because insomnia and sleep disorders are thought to be caused by a shortage of NAT enzymes in the pineal gland, a novel treatment strategy to sleep disorders can be envisaged by administering such hypnotic acetyl metabolites of melatonin, or synthetic analogs thereof.

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Nighttime melatonin release is temporally related with sleep in higher vertebrates that are active during the day (e.g., humans, chicks, and dogs, but not rats, who are nocturnal). The analysis of 24-hour urine samples from young and old adults with and without insomnia (Figure 1) reveals a clear relationship between sleep and urinary excretion of 6-sulfatoxymelatonin. 1 Insomniacs have much lower melatonin synthesis from the pineal gland, which is attributed to a drop in the quantity of the enzyme serotonin Af-acetyltransferase (NAT). Insomnia may be caused by a deficiency of this NAT enzyme in the pineal gland.