2-取代的1,3,4-噻二唑-5-磺酰胺类作为碳酸酐酶抑制剂：它们对离体兔睫状体跨上皮电位差及对活体兔眼眼压的影响。

2-Substituted 1, 3, 4-thiadiazole-5-sulfonamides as carbonic anhydrase inhibitors: their effects on the transepithelial potential difference of the isolated rabbit ciliary body and on the intraocular pressure of the living rabbit eye.

作者信息

Kishida K, Miwa Y, Iwata C

出版信息

Exp Eye Res. 1986 Dec;43(6):981-95. doi: 10.1016/0014-4835(86)90076-x.

Abstract

In order to understand the pharmacology of carbonic anhydrase inhibitors in reduction of aqueous secretion, three sorts of studies were conducted using five 2-substituted 1, 3, 4-thiadiazole-5-sulfonamides: an inhibition study of carbonic anhydrase II, electrical measurements of the isolated ciliary body, and pharmacological study on intraocular pressure of living animals. The inhibitors of carbonic anhydrase employed here were 2-amino-1, 3, 4-thiadiazole-5-sulfonamide; 2-methylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-formylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-acetylamino-1, 3, 4-thiadiazole-5-sulfonamide (acetazolamide); and 2-propionylamino-1, 3, 4-thiadiazole-5-sulfonamide. All of these compounds showed significant inhibitory activity to carbonic anhydrase II which exists in the ciliary epithelium, but their potencies of inhibition varied relative to one another (I50S were 1.91 X 10(-7) to 3.3 X 10(-8) M). The effects of the five compounds on electrical phenomena were observed using isolated rabbit ciliary body mounted on an Ussing's chamber. Each compound decreased the negative electrical potential of the tissue (-0.70 mV as the average of the initial values) by 10- to 33%, and this effect was proportional to its inhibitory activity to carbonic anhydrase II. The effects of the five compounds on intraocular pressure were determined, and each compound decreased the intraocular pressure (18 mmHg as the average of the initial values) by 7- to 32%. This effect was also proportional to the inhibitory activity to the enzyme. Correlation between the two effects was studied, and good correlation was observed. This implies that both effects have a common basis which relates to the physiological role of carbonic anhydrase. The present study, therefore, shows the importance of the bicarbonate ion in the aqueous humor formation since it is both substrate and product of carbonic anhydrase II.

摘要

为了了解碳酸酐酶抑制剂在减少房水分泌方面的药理学特性，使用五种2-取代的1,3,4-噻二唑-5-磺酰胺进行了三类研究：碳酸酐酶II的抑制研究、离体睫状体的电测量以及对活体动物眼压的药理学研究。这里使用的碳酸酐酶抑制剂有2-氨基-1,3,4-噻二唑-5-磺酰胺；2-甲氨基-1,3,4-噻二唑-5-磺酰胺；2-甲酰氨基-1,3,4-噻二唑-5-磺酰胺；2-乙酰氨基-1,3,4-噻二唑-5-磺酰胺（乙酰唑胺）；以及2-丙酰氨基-1,3,4-噻二唑-5-磺酰胺。所有这些化合物对存在于睫状体上皮中的碳酸酐酶II均表现出显著的抑制活性，但它们的抑制效力彼此不同（半数抑制浓度为1.91×10⁻⁷至3.3×10⁻⁸M）。使用安装在尤斯室上的离体兔睫状体观察了这五种化合物对电现象的影响。每种化合物使组织的负电位（初始值的平均值为-0.70mV）降低了10%至33%，并且这种作用与其对碳酸酐酶II的抑制活性成正比。测定了这五种化合物对眼压的影响，每种化合物使眼压（初始值的平均值为18mmHg）降低了7%至32%。这种作用也与对该酶的抑制活性成正比。研究了这两种作用之间的相关性，并观察到良好的相关性。这意味着这两种作用有一个与碳酸酐酶的生理作用相关的共同基础。因此，本研究表明碳酸氢根离子在房水形成中的重要性，因为它既是碳酸酐酶II的底物又是其产物。