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- W1996352213 abstract "The carbonic anhydrase (C.A.) inhibitor, L-650,719 (6-hydroxy-benzo[b]thiophene-2-sulfonamide) is an advance over the corresponding 6-OH benzothJazole-2-sulfonamide in increased water solubility (4 mM) and CHCl3/buffer partition (0.05). KI vs CA is 10−8 M. Topical treatment with 1 drop of 0.15-8% suspensions (in hydroxyethylcellulose-HEC) lowered intraocular pressure (IOP) up to 2.6 mmHg, with a plateau at 2%. Two hours after 2% treatment ocular drug distribution showed (μM or μmole/kg): cornea, 115, anterior aqueous 27, posterior aqueous 4, ciliary processes 15. Calculated inhibition of C.A. is 99.7%. IOP lowering effect disappeared at 6 hrs. L-650,719 was also given in solution (17 mM, pH 9.3). One drop every 5 min × 5 or 10 min residence on cornea of this solution produced an IOP lowering and drug distribution similar to that of the 2% suspension. Increasing HEC concentration in the single drop solution from 0 to 1%, led to a 3-fold increase in anterior aqueous drug levels and an improved ΔIOP. The pressure lowering is somewhat less than achieved with parenteral sulfonamides in the rabbit. Clinical trials showed modest activity, so L-650,719 is not being developed further. It is evident, however, that sulfonamides with a variety of chemical and pharmacological properties are conducive to development for topical treatment of glaucoma." @default.
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- W1996352213 date "1989-01-01" @default.
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- W1996352213 title "Ocular Hypotensive Activity and Disposition of the Topical Carbonic Anhydrase Inhibitor 6-Hydroxy-Benzo[b]Thiophene-2-Sulfonamide, L-650,719, in the Rabbit" @default.
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- W1996352213 doi "https://doi.org/10.1089/jop.1989.5.99" @default.
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