Acetazolamide for the Treatment of Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is characterized by an increase of intracranial pressure in the absence of neurologic tumors. The sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor (CAI) acetazolamide (AAZ), a compound developed in the 1950s as a diuretic drug and presently used as an antiglaucoma, antiepileptic and diuretic agent, is effective in the treatment of IIH. AAZ is a low nanomolar inhibitor of CA isoforms involved in cerebrospinal fluid (CSF) secretion. Inhibition of brain/choroid plexus CA II, IV, VA and XII leads to a decreased CSF fluid secretion and control of the intracranial pressure. Although many sulfonamide/sulfamate CAIs are in clinical use for decades, apparently only AAZ is being currently used clinically for IIH. We speculate that more lipophilic CAIs such as methazolamide, zonisamide or topiramate should lead to a more effective control of increased intracranial pressure, thus having the opportunity to become useful in the management of IIH.