Carbonic anhydrase inhibitors - Part 52. Metal complexes of heterocyclic sulfonamides: A new class of strong topical intraocular pressure-lowering agents in rabbits

A new sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties has been prepared by reaction of 5-amino-1,3,4-thiadiazole-2- sulfonamide with adamantyl-1-carboxylic acid chloride. Metal complexes of the adamantyl derivative, containing di- and trivalent cations, were also obtained and characterized by standard procedures. Although the parent sulfonamide does not possess topical pressure-lowering effects in rabbits when applied as a 2% solution directly into the eye, some of its metal complexes, such as the Zn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals better than dorzolamide, the topical sulfonamide with strong antiglaucoma action, recently introduced in clinical medicine. We propose here that the whole class of metal complexes of heterocyclic sulfonamides (which generally possess much stronger CA inhibitory properties as compared to the original sulfonamides from which they were prepared) might be used for lowering IOP with enhanced efficiencies as compared to those of the simple sulfonamides. Thus, metal complexes of sulfonamides possessing themselves topical antiglaucoma properties might lead to more effective pharmacological agents of this type.