|Trade names||Zonegran, others|
|Main uses||Epilepsy (partial seizures)|
|Side effects||Abdominal pain, nausea, constipation, dry mouth, dizziness|
|Metabolism||Liver through CYP3A4|
|Elimination half-life||63 hours in plasma|
|Excretion||Kidney (62%); Faeces (3%)|
|Chemical and physical data|
|Molar mass||212.22 g·mol−1|
|3D model (JSmol)|
|Melting point||162 °C (324 °F)|
Zonisamide, sold under the brand name Zonegran, is a medication used in addition to other medications to treat epilepsy, specifically partial seizures. There is also some evidence for its use in Parkinson's. It is taken by mouth.
Common side effects include abdominal pain, nausea, constipation, dry mouth, and dizziness. Other side effects may include hair loss, nystagmus, and bone marrow disorders. Use during pregnancy may harm the baby and use during breastfeeding is not recommended. It is in the sulfonamide family of chemicals and is not recommended in people allergic to these.
Zonisamide was approved for medical use in the United States in 2000. It is available as a generic medication. In the United States it costs less than 20 USD per month as of 2021. It is also relatively inexpensive in the United Kingdom.
In Japan it is also used for generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.
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. In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009. 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.
Very common (>10% incidence)
Common (1-10% incidence)
- Affect lability
- Psychotic disorder
- Disturbance in attention
- Speech disorder
- Abdominal pain
- Influenza-like illness
- Oedema peripheral
- Weight loss
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. Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.
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.
Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.
Mechanism of action
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). 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.
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.
Zonisamide was discovered by Uno and colleagues in 1972 and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan. 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. Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others) and Europe (starting in Germany and the United Kingdom).
Society and culture
The cost of this medication in the U.S. is $30 (USD) for 100 capsules (100 mg) 
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