CNS Drug Reviews, Vol. 4, No. 4, Winter 1998

The discovery of zonisamide (ZNS) did not result from a search for new antiepileptic drug (AED). A continuous random screening for anticonvulsant activity had been in progress for many years at the research laboratories of Dainippon Pharmaceutical Co., Ltd. ZNS was discovered by serendipity in 1974 during routine testing of 1,2-benzisoxazole derivatives which were synthesized for the management of psychiatric diseases (49,101). Among the derivatives tested, some compounds including ZNS, were found to have a potent anticonvulsant activity in experimental animals. ZNS has a benzisoxazole structure that distinctly differs from any existing AED. The chemical structure of ZNS is shown in Fig. 1. After comprehensive preclinical studies, clinical development of ZNS in Japan started in September 1979. ZNS was approved for the control of partial seizures and generalized seizures in March and launched in June, 1989, in Japan. ZNS was introduced to the Korean market in 1992. In the United States, a New Drug Application (NDA) was submitted in March 1997. The Food and Drug Administration (FDA) issued an approvable letter to the company in March, 1998, for use as adjunctive therapy in the treatment of partial seizures in adults with epilepsy (80). This review will focus mainly on the pharmacodynamic properties of ZNS and its clinical efficacy in epilepsy.