Acetazolamide for the treatment of idiopathic intracranial hypertension

Abstract

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.

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

“…The last CA class was discovered recently analyzing the amino acid sequences of CAs from Plasmodia 5,[7][8][9][10][11] . The a-, b-, d-and Z-CAs use Zn(II) ions at the active site, the g-CAs are probably Fe(II) enzymes (but they are active also with bound Zn(II) or Co(II) ions), whereas the z-class are cambialistic enzymes, active both with Cd(II) or Zn(II) bound within the active site 3,4,[12][13][14][15][16][17][18][19] . The metal ion from the enzyme active site is coordinated by three histidine (His) residues (in the a-, g-d-class enzymes) or by one His, and two cysteine (Cys) residues (in the band z-CAs), with the fourth ligand being a water molecule/ hydroxide ion acting as nucleophile in the catalytic cycle of the enzyme.…”

Shunt Surgery in Idiopathic Intracranial Hypertension Aided by Electromagnetic Navigation

“…Diagnostic criteria have been updated by Friedman and Jacobson [3], and, in general, there is no specific underlying cause. Although the pathophysiology is still unknown, many patients benefit from medical treatment with acetazolamide [7,8]. Surgical treatment is indicated in patients with persistent headache and visual deterioration.…”

“…There are several surgical options available including optic nerve sheath fenestration, venous stenting and CSF diversion [8,9,10,11]. Because of the usually small size of the ventricles and the resulting difficulty in targeting for placement of the proximal catheter, lumboperitoneal shunting had been favored by many investigators for CSF diversion in IIH for decades.…”

Design, synthesis and biological evaluation ofN-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors

“…Several other CAIs such as ethoxolamide (EZA), brinzolamide (BRZ), dorzolamide (DZA), methazolamide (MZA), and dichlorophenamide (DCP) are useful clinically as antiglaucoma agents but, they are also used to treat various neurological as well as neuromuscular disorders such as epilepsy, genetic hemiplegic migraine and ataxia, tardive diskinesia, hypokalemic periodic paralysis, essential tremor and Parkinsons disease 13 . Unfortunately, the presently used CAIs are non-selective to a particular CA isoform, which leads to the occurrence of peripheral side effects.…”