Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects

To clarify whether the inhibitory effect of zonisamide (Excegran, CAS 68291-97-4) on carbonic anhydrase contributes to its anticonvulsant activity, the anticonvulsant activity of 7-methylated zonisamide, a zonisamide analogue which has the same potency of activity as zonisamide in inhibiting carbonic anhydrase in vitro, has been examined. The study using mice did not reveal 7-methylated zonisamide to have any anticonvulsant activity even though its brain concentration level was more than two times the minimal effective concentration of zonisamide. These findings indicate that the anticonvulsant effect of zonisamide is derived from a mechanism(s) other than inhibition of carbonic anhydrase.