Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase inhibitory activity:: Drug design and mechanism of action

The marketed antiepileptic drugs can not solve entirely the problem of seizure in patients suffering from refractory epilepsies. Therefore, new anticonvulsant compounds structurally and pharmacologically different of the currently prescribed drugs are needed. Carbonic anhydrase (CA) inhibitors are known to act as anticonvulsant since several decades while the link between CA and seizure is not straightforward. However, the recent discovery that several CA isozymes are expressed in brain and the better knowledge of their physiological/pathological role, lead to the emergence of new CA inhibitors with anticonvulsant effect including: analogues of acetazolamide, analogues of topiramate, aromatic or heterocyclic sulfonamides incorporating valproyl or adamantyl moieties. Different strategies are developed for the design of new more selective CA inhibitors with anticonvulsant properties.