Phenytoin interacts with calcium channels in brain membranes.

Phenytoin at concentrations of between 30 and 300 microM inhibited binding of the calcium antagonist [3H] nitrendipine to voltage-dependent calcium channels in brain membranes. Other anticonvulsants (phenobarbital, carbamazepine, valproic acid, and clonazepam) failed to inhibit binding or did so only at concentrations much higher than occur clinically. Calcium channel blockade may be important in the clinical actions of phenytoin, including certain of the adverse effects of the drug.