BASIS OF THE ANTISEIZURE ACTION OF PHENYTOIN

1. Phenytoin has been used with much clinical success against all type s of epileptiform seizures, except petit mal epilepsy, for over 50 yea rs. Its mechanism of action, however, is still open to interpretation. 2. Several potential targets for phenytoin action have been identifie d within the central nervous system. These include the Na-K-ATPase, th e GABA(A) receptor complex, ionotropic glutamate receptors, calcium ch annels and sigma binding sites. 3. To date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plas ma membrane of neurons undergoing seizure activity, Quieter nerve cell s are far less affected. Moreover, the fact that phenytoin also has im portant cardiac antiarrthymic effects and can inhibit Na+ influx into cardiac cells supports the idea that the primary target of phenytoin i s, indeed, the Na+ channel. Copyright (C) 1996 Elsevier Science Inc.