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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002531:Cerebellum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002395:Catecholamines; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D004298:Dopamine; D009638:Norepinephrine