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 comple xes 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, eff ects in rabbits when applied as a 2% solution directly into the eye, s ome 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 who le class of metal complexes of heterocyclic sulfonamides (which genera lly 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 s imple sulfonamides. Thus, metal complexes of sulfonamides possessing t hemselves topical antiglaucoma properties might lead to more effective pharmacological agents of this type. (C) Elsevier, Paris.