Glaucoma and the applications of carbonic anhydrase inhibitors

Subcell Biochem. 2014;75:349-59. doi: 10.1007/978-94-007-7359-2_17.

Abstract

Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) has pharmacologic applications in the treatment of glaucoma, a disease affecting a large number of people and characterized by an elevated intraocular pressure (IOP). At least three isoforms, CA II, IV and XII are targeted by the sulfonamide inhibitors, some of which are clinically used drugs. Acetazolamide, methazolamide and dichlorophenamide are first generation CA inhibitors (CAIs) still used as systemic drugs for the management of this disease. Dorzolamide and brinzolamide represent the second generation inhibitors, being used topically, as eye drops, with less side effects compared to the first generation drugs. Third generation inhibitors have been developed by using the tail approach, but they did not reach the clinics yet. The most promising such derivatives are the sulfonamides incorporating either tails with nitric oxide releasing moieties or hybrid drugs possessing prostaglandin (PG) F agonist moieties in their molecules. Recently, the dithiocarbamates have also been described as CAIs possessing IOP lowering effects in animal models of glaucoma. CAIs are used alone or in combination with other drugs such as adrenergic agonist/antagonists, or PG analogs, being an important component of the antiglaucoma drugs armamentarium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetazolamide / therapeutic use
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase IV / antagonists & inhibitors
  • Carbonic Anhydrase IV / chemistry
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Glaucoma / drug therapy*
  • Glaucoma / pathology
  • Humans
  • Intraocular Pressure / drug effects
  • Nitric Oxide / chemistry
  • Structure-Activity Relationship*
  • Sulfanilamide
  • Sulfanilamides / therapeutic use*
  • Sulfonamides / therapeutic use
  • Thiazines / therapeutic use

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfanilamides
  • Sulfonamides
  • Thiazines
  • Sulfanilamide
  • Nitric Oxide
  • brinzolamide
  • Carbonic Anhydrase II
  • Carbonic Anhydrase IV
  • CA4 protein, human
  • Carbonic Anhydrases
  • carbonic anhydrase XII
  • Acetazolamide