Zonisamide is chemically classified as a sulfonamide. It is not related to any other seizure medicines.

The precise way that it works to control seizures (what doctors call the "mechanism of action") is unknown. Possible mechanisms may have something to do with the fact that it blocks sodium channels (the route by which sodium ions move in and out of nerve cells) and certain calcium channels. These effects may stabilize the membranes of nerve cells in the brain and prevent them from all firing together in an uncontrolled surge.

Zonisamide also slightly inhibits the action of an enzyme called carbonic anhydrase. Some other substances that have this action are effective against certain types of seizures, but this effect is not thought to be a major contributing factor in the antiseizure activity of zonisamide.