Abstract
The interaction between the anticonvulsant trimethadione and the convulsant metrazol on the metabolism of brain serotonin, was studied in rats. Trimethadione (400 mg kg ) alone produced a 28–44% increase in the rate of synthesis of brain serotonin. The same dose of trimethadione plus 30 or 50 mg kg of metrazol produced no change in the rate of synthesis of brain serotonin and no Scizures. Trimethadione plus 75 mg kg of metrazol produced a 55% decrease in the rate of synthesis of brain serotonin and a marked increase in locomotor activity, but no clonictonic scizures. Reserpine produced a 62% decrease in the mean convulsive dose of metrazol in rats treated with trimethadione. p-Chlorophenylanine produced a 26% decrease in mean convulsive dose, which was reversed by 5-hydroxytryptophan. Alpha-methyltyrosine and 5-hydroxytryptophan had no effect on mean convulsive dose. A comparison of these results with previous work in which the effect of metrazol alone on metabolism of brain serotonin was studied, suggests a definite correlation between the changes in brain serotonin metabolism seen after metrazol and trimethadione and their convulsive and anticonvulsive action, respectively.
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