化合物信息

Drug Groups

approved; investigational

Description

Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may be a carbonic anhydrase inhibitor although this is not one of the primary mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels leading to a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.

Indication

For use as adjunctive treatment of partial seizures in adults with epilepsy.

Pharmacology

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).

Toxicity

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

Affected Organisms

Biotransformation

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.

Absorption

Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.

Half Life

63 hours

Protein Binding

40% (at concentrations of 1.0-7.0 µg/mL)

Elimination

Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.

Distribution

* 1.45 L/kg

Clearance

* 0.30 - 0.35 mL/min/kg [patients not receiving enzyme-inducing antiepilepsy drugs (AEDs)]
* 0.35 - 0.5 mL/min/kg [Concomitant administration of phenytoin and carbamazepine]

References

External Links