Inhibition of Serum Melatonin Concentration and Synthesis of Brain Indolealkylamines by Monofluoromethyldopa in the Rat

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Abstract
The simultaneous effect of .alpha.-monofluoromethyldopa (MEMD) on the synthesis of rat brain indolealkylamines was investigated in daytime and in dark phase. The effect on serum melatonin concentration was also determined in the dark period. MFMD inhibits 5-hydroxytryptophan decarboxylase in the pineal gland, hypothalamus and cerebral cortex. Simultaneous measurement of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and 5-hydroxyIAA (5-HIAA) levels in the 3 brain areas revealed that MFMD caused large increases in pineal 5-HTP concentrations and substantial decreases in pineal 5-HT and 5-HIAA in the light and dark phases. A significant decrease in daytime hypothalamic 5-HT content after 7-h pretreatment and a large increase in dark-phase cortical 5-HT concentration after 4-h pretreatment was demonstrated. Serum melatonin levels were also reduced by the action of MFMD in the dark period. Differences evidently occur in the rate-limiting steps in the indolealkylamine biosynthesis in the 3 brain areas.