ABSTRACT
Zonisamide (ZNS) is a sulfonamide derivative, 3-sulfamoylmethyl-l,2-benzisoxazole (or 1,2-benzisoxazole-3-methanesulfonamide), which has also been termed AD-810 and CI-912. Rodent maximal electroshock and pentylenetetrazol models demonstrate an antiepileptic profile of ZNS similar to those of phenytoin and carbamazepine, with greater efficacy of ZNS against tonic than clonic phases of proconvulsant-induced seizures. Autoradiographic studies demonstrate high-affinity, specific binding of ZNS at a site which may be in the benzodiazepine/gamma aminobutyric acid chloride-channel complex. Distribution of ZNS is complex, demonstrating variation in volume of distribution with dose, plasma protein binding, and significant erythrocyte binding. ZNS probably has a single major metabolite in man, a glucuronide; an acetylated metabolite has also been demonstrated. ZNS has usually been used adjunctively but has multiple interactions with other antiepileptic drugs (AEDs). In general, administration of other AEDs concurrently increases clearance of ZNS. Increase in clearance of ZNS is greater, at least for single doses of ZNS, on PHT than on CBZ therapies chronically.
