The study of ocular hypotensive effect of 6-hydroxyethoxy-2-benzothiazole sulfonamide: a topical carbonic anhydrase inhibitor.
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 microL of 3% 6-HS gel, but a dose of 50 microL 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.
Lu
D W
DW
Department of Ophthalmology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chiang
C H
CH
Kao
K D
KD
Wen
L Y
LY
D000818:Animals; D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002918:Chymotrypsin; D004195:Disease Models, Animal; D005016:Ethoxzolamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D005260:Female; D005901:Glaucoma / Q000503:physiopathology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D011817:Rabbits
D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors; C043694:6-hydroxyethoxzolamide; D002918:Chymotrypsin; D005016:Ethoxzolamide