Phenytoin and cerebellar lesions. Similar effects on cerebral catecholamine metabolism

Phenytoin has been shown to inhibit catecholamine (CA) metabolism in vitro. The present investigation examined its longer-term in vivo effects in rats. Phenytoin 100 mg/kg/day for two weeks, caused an increase in hindbrain norepinephrine (NE) concentration, a slight decrease in forebrain NE concentration, and little change in dopamine (DA) levels. The turnover rates of forebrain DA and NE estimated by synthesis inhibition, were increased by 70% and 100%, respectively. Surgical lesions of the anterior cerebellar vermis produced similar (but not additive) increases in turnover. It is concluded that long-term phenytoin use stimulates CA metabolism in the forebrain and that this effect may be mediated indirectly by the cerebellar vermis.