Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans.
To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of human melatonin production, we studied the effects of the acute administration of the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24-33 years, underwent three experimental sessions in which they received orally 400 mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind design. The drug administration was done at 19:00 hours; thereafter, blood samples were collected over the night, in dark conditions with the help of a red light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one. The maximum suppression coincided with the highest plasma levels of valproic acid. These findings support the view that endogenous GABA may participate in the modulation of the activity of the human pineal gland.
Monteleone
P
P
Institute of Psychiatry, School of Medicine, Second University of Naples, Italy.
Tortorella
A
A
Borriello
R
R
Natale
M
M
Cassandro
P
P
Maj
M
M
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D003864:Depression, Chemical; D004311:Double-Blind Method; D017248:Enzyme Multiplied Immunoassay Technique; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood*; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D008550:Melatonin