<p>The precise mechanism(s) by which zonisamide exerts its antiseizure effect is unknown. Zonisamide demonstrated&nbsp;anticonvulsant&nbsp;activity in several experimental models. In animals, zonisamide was effective against tonic&nbsp;extension&nbsp;seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol. Zonisamide raised the threshold for generalized seizures in the kindled rat model and reduced the duration of&nbsp;cortical&nbsp;focal&nbsp;seizures induced by electrical stimulation of the visual&nbsp;cortex&nbsp;in cats. Furthermore, zonisamide suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human&nbsp;epilepsy&nbsp;is unknown.<br />
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Zonisamide may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that zonisamide blocks sodium channels and reduces voltagedependent, transient inward currents (T-type Ca2+&nbsp;currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that zonisamide binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux. Other in vitro studies have demonstrated that zonisamide (10&ndash;30 &mu;g/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or&nbsp;glutamate&nbsp;responses (cultured mouse&nbsp;spinal cord&nbsp;neurons) or neuronal or glial uptake of [3H]-GABA (rat hippocampal slices). Thus, zonisamide does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that zonisamide facilitates both dopaminergic and serotonergic neurotransmission.<br />
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Zonisamide is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of zonisamide is unknown. However, as a carbonic anhydrase inhibitor, zonisamide may cause metabolic&nbsp;acidosis</p>