著者
MICHINORI KABUTO IKUO NAMURA YOUICHI SAITOH
出版者
The Japan Endocrine Society
雑誌
Endocrinologia Japonica (ISSN:00137219)
巻号頁・発行日
vol.33, no.3, pp.405-414, 1986 (Released:2011-01-25)
参考文献数
14
被引用文献数
35 44

Plasma melatonin levels were determined every 20 and 30min for 24 hours on the last day of repeated oral administrations (1 or 2mg a day for 8 or 9 days) of a benzodiazepine derivative (450191-s), which is known to be metabolized to active benzodiazepines after administration. In one of the two subjects, the nocturnal enhancement of plasma melatonin which was obvious on a control day with placebo was diminished almost completely. In the other subject, observed were not only the diminishment of its nocturnal enhancement but also its increase during the daytime almost to the nocturnal levels on a control day, which may indicate a rebound increase in melatonin synthesis or a shift in its day-night rhythmicity.Such suppressing effects of benzodiazepines on the nocturnal plasma melatonin levels were also examined in the case of a single administration of 2mg of 450191-s or flunitrazepam in the second series of experiments. Even a single flunitrazepam seemed to have lowered nocturnal plasma melatonin levels, which then recovered to the usual levels following the administration of 5mg of a benzodiazepine antagonist, Ro 15-1788, given 6 hours after the flunitrazepam. However, single 450191-s did not show any remarkable effects.Thus, it has been suggested that benzodiazepines could suppress the nocturnal levels of plasma melatonin or shift its day-night rhythmicity at least when administered repeatedly. The possible action site of benzodiazepines may be the central nervous system, since melatonin synthesis has been thought to be under strongly regulated by the central nervous pathway from the retina to the pineal body. Therefore, these effects of benzodiazepines may provide a method for investigating the physiological role of melatonin and its day-night rhythmicity as well as to further clarify the system regulating melatonin synthesis in humans.