Zonisamide

Zonisamide is a sulfonamide derivative with an anticonvulsant property. The exact mechanism of action remains to be elucidated. Zonisamide appears to block sodium and calcium channels, thereby stabilizing neuronal membranes and suppressing neuronal hyper-synchronization. Although zonisamide shows affinity for the gamma-aminobutyric acid (GABA)/benzodiazepine receptor ionophore complex, it does not potentiate the synaptic activity of GABA. In addition, this agent also facilitates both dopaminergic and serotonergic neurotransmission.

Zonisamide is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. Preclinical studies have reported a range of potential mechanisms of action for zonisamide, such as blocking voltage-gated sodium channels, reduction of T-type calcium channel currents, and enhancement of gamma-aminobutyric acid (GABA)-mediated inhibition, which are indicative of its broad antiseizure effects. Zonisamide has a favorable linear pharmacokinetic profile, a long half-life, and a low incidence of protein-binding interactions with other AEDs.

Wilfong, A. A., & Willmore, L. J. (2006). Zonisamide–a review of experience and use in partial seizures. Neuropsychiatric disease and treatment, 2(3), 269.

The limitations of currently available therapies in addressing the non motor symptoms of Parkinson's disease (PD) have egged on the search for newer options. Zonisamide has been in use for epilepsy and it was serendipitously found to improve the symptoms of PD in a patient who had both epilepsy and PD. Thereafter, various trials were designed to assess the use of zonisamide in PD. The present article investigates the evidence for use of zonisamide in PD from the various clinical trials that were designed to address this issue. Furthermore, the article also summarizes the various mechanisms of its use in PD as described in various animal experiments.

Grover, N. D., Limaye, R. P., Gokhale, D. V., & Patil, T. R. (2013). Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson's disease. Indian journal of pharmacology, 45(6), 547.

Epilepsy is one of the most common neurologic disorders, affecting about 50 million people around the world. It is recognized that around 50% of patients with newly diagnosed epilepsy become seizure-free with the first drug treatment, so the choice of first antiepileptic drug is crucial. This paper provides a comprehensive overview of zonisamide as monotherapy for partial seizures, with special attention to the possibility of a once-daily regimen. The available data suggest that zonisamide is an effective and well tolerated option as monotherapy.

Mula, M. (2013). Profile of once-daily zonisamide as monotherapy for treatment of partial seizures in adults. Drug design, development and therapy, 7, 397.