Melatonin - Circadian rhythms

Timing of melatonin secretion
Melatonin secretion increases shortly before sleep, usually around 9.00–10.00 pm. The peak nocturnal level in adults is reached between 3.00 and 5.00 am, which is around the transition point of the phase response curve to light. This is usually around 4h before waking in young subjects and 3h in the elderly but varies with the Chronotype.

Pharmacology of melatonin
Melatonin is lipid soluble and is released both into the cerebrospinal fluid and into the blood so that it becomes widely distributed within the brain and the rest of the body, to which it acts as an indirect chemical messenger of the SCN. The concentration in the periventricular areas of the brain, which are exposed to the cerebrospinal fluid, may be very much higher than the blood levels.

Melatonin has a half-life of 30–45min in the blood and is mainly inactivated in the liver by conversion
to 6-hydroxymelatonin. It is then conjugated with sulphuric or glucuronic acid. These metabolites are excreted in the urine, particularly 6-sulphatoxymelatonin whose concentration runs in parallel, but with a delay of around 1h behind the serum melatonin concentration.

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