Lu D W, Chiang C H, Kao K D, Wen L Y
Department of Ophthalmology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
J Ocul Pharmacol. 1990 Winter;6(4):271-8. doi: 10.1089/jop.1990.6.271.
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.
一种新合成的局部碳酸酐酶抑制剂6-羟基乙氧基-2-苯并噻唑磺酰胺(6-HS),通过全身给药和局部给药的方式作用于α-糜蛋白酶诱导的青光眼兔,以评估其降眼压效果。局部应用50微升3%的6-HS凝胶后观察到显著的眼压降低效果,但50微升3%的6-HS混悬液未能降低眼压。局部滴注凝胶后眼压降低的最大幅度为24.4%,与静脉注射6毫克/千克的6-HS后得到的结果(23.3%)非常接近。然而,局部滴注3%的6-HS凝胶后6-HS的血药浓度远低于静脉注射6毫克/千克的6-HS后的血药浓度(小于5%)。由于静脉注射较低剂量的6-HS(1毫克/千克)并未导致眼压显著下降,因此可以合理推断局部应用6-HS的降眼压作用可归因于眼内碳酸酐酶活性的抑制。还注意到,静脉注射较大剂量的6-HS(20毫克/千克)具有更显著的降低眼压和血压的作用,并伴有中度代谢性酸中毒。