A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-HS), was administered systemically and topically to alpha-chymotrypsin-induced glaucoma rabbits to evaluate its ocular hypotensive effect. A significant IOP lowering effect was observed after topical application of 50 pi of 3% 6-HS gel, but a dose of 50 p.1 of 3% 6-HS suspension failed to reduce IOP. The maximal magnitude of reduced IOP after topical gel instillation was 24.4%, very close to the result obtained following intravenous injection of 6 mg/Kg of 6-HS (23.3%). However, the blood levels of 6-HS after topical instillation with 3% 6-HS gel was much lower than that following 6 mg/Kg of 6-HS injected intravenously (less than 5%). Since a lower dose of 6-HS (1 mg/Kg) administered intravenously did not cause a significant drop in IOP, it is reasonable to deduct that the ocular hypotensive effect of 6-HS applied topically can then be attributed to the inhibition of intraocular carbonic anhydrase activity. It was also noted that a larger dose of intravenous administration of 6-HS (20 mg/Kg) had a more profound IOP and blood pressure reducing effect with moderate metabolic acidosis.

A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2benzothiazole sulfonamide (6-HS), was used as a model drug to determine its corneal and scierai permeabilities in rabbit eyes. The corneal permeability coefficient of 6-HS for short duration glaucoma and normal rabbit eye was not significantly different (its mean value was around 2.9 x 10" cm/sec), while the corneal permeability coefficient for long duration glaucoma rabbit eye was 1.8 times greater than that for the normal eye. The sciera was found to have a higher permeability than the cornea in that after four hours perfusion the amount of drug which passed through the sciera was 11 times greater than that of the cornea.In addition, it was also noted that after topical instillation of 50 uL of 3% 6-HS gel the aqueous humor concentrations of 6-HS in short duration glaucoma eye and normal eye were not statistically different.