Basis of the antiseizure action of phenytoin.
1. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy, for over 50 years. Its mechanism of action, however, is still open to interpretation. 2. Several potential targets for phenytoin action have been identified within the central nervous system. These include the Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites. 3. To date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plasma membrane of neurons undergoing seizure activity. Quieter nerve cells are far less affected. Moreover, the fact that phenytoin also has important cardiac antiarrhythymic effects and can inhibit Na+ influx into cardiac cells supports the idea that the primary target of phenytoin is, indeed, the Na+ channel.
Tunnicliff
G
G
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville 47712, USA. GTUNNIC@INDYVAX.IUPUI.EDU
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D015222:Sodium Channels; D010672:Phenytoin