Effects of phenytoin on convulsions and on brain 5 hydroxytryptamine and 5-hydroxyindoleacetic acid levels in El mice

Phenytoin (PHT) metabolism and brain monoamine levels were examined daily after chronic administration of 40mg/kg/day of PHT-Na into ddY mice. The blood PHT level increased remarkably the first day and then tended to decrease, attaining a transitory minimum on the third day of a 7-day experiment. The half-life of PHT after a single injection was about 12 hours, and the administration of PHT for 3 days shortened the half-life to about 6 hours. The urinary excretion of 5-(p-hydroxyphenyl)-5-phenylhydantoin tended to increase from the first day and attained a maximum on the fourth day of a 7-day experiment. Levels of 5-hydroxytryptamine (5-HT) and catecholamine in the mouse brain increased transitorily from the third to sixth day of a 14-day experiment. On the 14th day, these levels remained at the control level. Effects of PHT on convulsions and on regional levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the El mouse brain were examined. PHT completely inhibited convulsions in El mice after intraperitoneal injections of 40mg/kg of PHT-Na twice a day for three days. After the injection of PHT twice a day for three days, the 5-HT level was increased in the striatum, hypothalamus, midbrain and pons-medulla oblongata, and the 5-HIAA level was increased in the cortex, hippocampus, midbrain, pons-medulla oblongata and cerebellum. These results suggest that the inhibitory effect of PHT on the convulsions may be based on the activation of the 5-HTergic neurone system in El mice.