Abstract
The effect of valproic acid (2- n-propyl-pentanoic acid) on serotonin metabolism was examined in rats and mice, since this anticonvulsant has beneficial therapeutic action on human myoclonic disorders which have been associated with brain serotonin deficiency. A single intraperitoneal injection of 400 mg/kg valproic acid decreased total serum tryptophan and increased free serum tryptophan, brain tryptophan and brain 5-hydroxyindoleacetic acid (5HIAA) but had no effect on brain serotonin levels. Brain tryptophan levels returned to normal in mice after chronic administration of valproic acid (400 mg/kg daily for 7 days) but the changes in serum tryptophan and brain 5HIAA persisted. Valproic acid potentiated the anti-myoclonic action of chlorimipramine in a p, p'-DDT-induced animal myoclonus model. Valproic acid may displace protein-bound serum tryptophan thereby increasing brain tryptophan which is converted to serotonin.
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