title: Carbonic anhydrase inhibitory activity and ocular pharmacology of organic sulfamates.
abstract: Organic sulfamates are a new variation to the carbonic anhydrase (CA) inhibitor structure-action relationship. Inhibitory activity is conferred by the classic sulfonamide group, but through linkage to the benzene ring by an oxygen. AHR-16329, a representative sulfamate, has an acidic (sulfonamide, pKa 8.9) and basic (imidazole, pKa 6.0) group and has desirable physicochemical properties for topical intraocular pressure lowering: good water solubility below pH 6.0, a CHCl3/buffer ratio of 0.5 at pH 7.0 and a Kl against CA-II of 7 nM. Inhibition of CO2 hydration is noncompetitive. When applied locally to the eye, AHR-16329 reaches significant levels in ocular tissues and fluids and reduces significantly intraocular pressure. Five percent concentration gives the greatest reduction, equivalent to systemic inhibitors; 2 and 5% have similar pressure x time duration. These studies expand structure-action relations in the field of CA inhibitors and the validity of developing topical CA inhibitors for treatment of glaucoma.
authors.affiliation: University of Florida Health Science Center, College of Medicine, Department of Pharmacology, Gainesville.
authors.forename: W F
authors.initials: WF
authors.lastname: Brechue
authors.forename: T H
authors.initials: TH
authors.lastname: Maren
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005123:Eye / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D013451:Sulfonic Acids / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007093:Imidazoles; D013449:Sulfonamides; D013451:Sulfonic Acids; D013876:Thiophenes; C079772:AHR 16329; C005741:sulfamic acid; C057921:sezolamide