Zonisamide binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity.

Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and calcium channels, which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid).

Primarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2_sulfamoylacetyl phenol, respectively.

Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.

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