The effects of the anticonvulsant valproic acid on cerebral indole amine metabolism.
The effects of valproic acid (500 mg/kg, ip, 1 h prior to testing) on indole amine metabolism were studied in rats by measurement of the contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral hemisphere. Tryptophan and 5-HIAA levels were increased, whereas 5-HTP and 5-HT remained unchanged. Furthermore, valproic acid failed to alter the levels of 5-HTP and DOPA, 5-HT and DA, and 5-HIAA in animals pretreated, respectively, with 3-hydroxybenzyl hydrazine (a decarboxylase inhibitor), pargyline (a monoamine oxidase inhibitor), or probenecid (a compound which blocks 5-HIAA transport out of the brain and cerebrospinal fluid). These results militate against the possibility that valproic acid alters the rate of tryptophan hydroxylation or the synthesis of 5-HT. However they do support the concept that valproic acid increases brain 5-HIAA by inhibition of the transport mechanism which removes 5-HIAA from the brain.
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D001679:Biogenic Amines; D007211:Indoles; D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D014635:Valproic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D004298:Dopamine