Diphenylhydantoin and calcium act antagonistically with respect to stimulus-coupled dl-norepinephrine-3H (NE3H) release from rat brain slices. Diphenylhydantoin also reduced calcium Ca 45 (45Ca) uptake into brain tissue. Procaine had a similar effect on NE3H release and 45Ca uptake; (hydroxyphenyl) phenylhydantoin, phenobarbital, and tetrodotoxin had no effect on either. Ouabain increased NE3H release and 45Ca uptake. The NE3H release from brain slices was sensitive to other circumstances that affect calcium movement: It was increased in low sodium media and decreased by high magnesium concentrations.
These results are compatible with the hypothesis that diphenylhydantoin acts like a local anesthetic and primarily limits membrane permeability to calcium.