Melatonin: from the hormone to the drug?

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland . It is synthesized at night under normal environmental conditions. The end ogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained by the light/dark cycle. Light is able to both suppress or synchr onize melatonin production according to the light schedule. The nycthohemer al rhythm of this hormone is determined by repeated measurement of plasma o r saliva MLT or urine sulfatoxymelatonin, the main hepatic metabolite. Mela tonin can be considered as the output (the hand) of the endogenous clock. S ince the regulating system follows central and sympathetic nervous pathways , an abnormality at any level unspecifically modifies the melatonin secreti on, especially in patients with sympathalgia or dysautonomia. Melatonin plays the role of an endogenous zeitgeber on sleep-wake cycle or core temperature. Exogenous melatonin is able to influence the endogenous s ecretion of the hormone according to a phase response curve. There are ther apeutic implications for this property in situations when biological rhythm s are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia i n blind or elderly people, shift-work). Improvement of pharmaceutical forms studied in controlled trials under the responsibility of the medical commu nity or development of melatonin analogs could lead to decisive progress in this field.