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Ball-and-stick model of the zonisamide molecule
Clinical data
Trade namesZonegran, Zonisade
License data
  • AU: D
Routes of
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding40%[5]
MetabolismLiver through CYP3A4[5]
Elimination half-life63 hours in plasma[5]
ExcretionKidney (62%); Faeces (3%)[5]
  • benzo[d]isoxazol-3-ylmethanesulfonamide
CAS Number
PubChem CID
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.118.526 Edit this at Wikidata
Chemical and physical data
Molar mass212.22 g·mol−1
3D model (JSmol)
Melting point162 °C (324 °F)
  • O=S(=O)(N)Cc2noc1ccccc12
  • InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12) checkY

Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease.[6][7] Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy in adults with Parkinson's disease, partial-onset seizures; infantile spasm, mixed seizure types of Lennox–Gastaut syndrome, myoclonic and generalized tonic clonic seizure.[8] Despite this it is also sometimes used as a monotherapy for partial-onset seizures.[7][9]

In 2020, it was the 276th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[10][11]

Medical uses[edit]


Zonisamide is approved in the United States,[2][12] and United Kingdom[13] for adjunctive treatment of partial seizures in adults and Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.[14] In Australia it is marketed as both an adjunctive therapy and monotherapy for partial seizures only.[9]

Parkinson's disease[edit]

It has been approved for the treatment of the motor symptoms of Parkinson's disease (PD), as an adjunct to levodopa, in a few countries such as Japan.[6][7] In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009.[15] In addition, there is clinical evidence that zonisamide in combination with levodopa control of motor symptoms of PD but evidence for the treatment of the non motor symptoms of PD lacking.[16][17]

Adverse effects[edit]

Adverse effects by incidence:[5][18][19]

Very common (>10% incidence) adverse effects include:

  • Anorexia
  • Somnolence
  • Dizziness
  • Agitation
  • Irritability
  • Confusional state
  • Depression
  • Diplopia
  • Memory impairment
  • Decreased bicarbonate

Common (1–10% incidence) adverse effects include:

Incidence unknown

  • Reproductive toxic effects[20]


Zonisamide and other carbonic anhydrase inhibitors such as topiramate, furosemide, and hydrochlorothiazide have been known to interfere with amobarbital, which has led to inadequate anesthetization during the Wada test.[21] Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.[5]

Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.[22]

Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.[23]

Mechanism of action[edit]

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 T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity).[9] It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). It is also known to modulate GABAergic and glutamatergic neurotransmission.[9][24][25][26][27]



Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8–3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption.[28][23]


Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5,[29] to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.[30]


Zonisamide was discovered by Uno and colleagues in 1972[31] and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan.[32] It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004.[33] Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)[34] and Europe (starting in Germany and the United Kingdom).[35]


Tardive dyskinesia[edit]

In an open-label trial zonisamide attenuated the symptoms of tardive dyskinesia.[36]


It has also been studied for obesity[37] with significant positive effects on body weight loss and there are three ongoing clinical trials for this indication.[38][39][40] It was to be sold, when combined with bupropion, under the brand name Empatic, until its development was discontinued.[41]


Zonisamide has been studied for and used as a migraine preventative medication, when topiramate is either ineffective or cannot be continued due to side effects.[7]

Bipolar depression[edit]

It has also been used off-label by psychiatrists as a mood stabilizer to treat bipolar depression.[42][43]


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