Induction for Deep Sleep
Arichive : Induction for Deep Sleep
Pharmacokinetic studies of melatonin in young and elderly human volunteers, and the measurement of hypnotic effects in chicks under alternate light-dark or permanent light conditions, show that 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), which are present in the pineal gland. The acetyl metabolite of melatonin, which we call carbo2, is an N-acetyl-β-carboline. The electroencephalographs (EEG) architecture of the sleep produced by this compound is similar to thai of physiological sleep, and is characterized by the significant proportion of slow-wave deep sleep and rapid eye movement sleep. This is in sharp contrast to the EEG sleep architecture observed with GABAergic (GABA, γ-aminobutyric acid) compounds. Since insomnia and sleep disorders are believed to be due to a lack of NAT enzymes in the pineal gland, a new therapeutic approach of sleep disorders by administration of such hypnotic acetyl metabolites of melatonin, or synthetic analogs thereof, can be en visaged.
In higher vertebrates that are active during the day (eg, humans, chicks, and dogs, but not rats, which are nocturnal), nighttime melatonin secretion is temporally associated with sleep. Analysis of 24-h urine samples from young and elderly people alike (Figure 1), with or without insomnia, clearly shows a direct correlation between sleep and urinary excretion of 6-sulfatoxymelatonin.1 Subjects with insomnia have a considerably reduced production of melatonin from their pineal gland, which is due to a decrease in the level of the enzyme serotonin Af-acetyltransferase (NAT). Insomnia could therefore be due to a lack of this NAT enzyme in the pineal gland.