Basis of the antiseizure action of phenytoin

• Published in: General Pharmacology 1996-10, Vol.27 (7), p.1091-1097
• Main Author: Tunnicliff, G.
• Format: Article
• Language: English
• Subjects: Animals; anticonvulsant; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Central Nervous System - cytology; Central Nervous System - drug effects; Central Nervous System - enzymology; epilepsy; Epilepsy - drug therapy; Epilepsy - physiopathology; GABA; Humans; Medical sciences; Na + channels; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Phenytoin; Phenytoin - pharmacology; Phenytoin - therapeutic use; Sodium Channels - drug effects; Sodium Channels - metabolism
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(96)00062-6

1. 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. 2. Several potential targets for phenytoin action have been identified within the central nervous system. These include the Na-K-ATPase, the GABA A receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites. 3. 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 antiarrthymic effects and can inhibit Na + influx into cardiac cells supports the idea that the primary target of phenytoin is, indeed, the Na + channel.