GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION

拟议的工作分为四个相关的类别，所有这些类别都是一致的 关于青光眼的房水形成和治疗问题： 开发新药(外用碳酸酐酶抑制剂)；研究 水的分泌物的离子反应.影响的探讨 A1C13和其他酸对睫状突的房水分泌和pH的影响； 自主神经药物和Na-K-ATPase抑制剂对电解质的影响 从血浆到水的运动。 1)我们正在寻找一种局部使用的碳酸酐酶抑制剂 1滴溶液即可降低眼压的特性 男人6-12个小时。这需要在有机合成方面继续努力， 化合物和水的物理化学性质的分析 动物和人类的动力学。这一目标的可行性似乎是合理的；它 已经在兔子身上实现了。几乎可以肯定的是，这样的化合物 对人体没有全身性毒性，也不会对眼睛有任何其他影响。 2.)我们相信这是可能的(有可能吗？)在房水中(和其他 分泌部位，如脑脊液和胰腺)，观察到的联系 Na+和HCO3-的离子配对具有特定的化学基础，NaCO3-的离子配对 和NaHCO3度。这还没有被认为是上皮分泌物。 但已被认为是红细胞中HCO3--Cl-交换的基础。 在这个观点中，Na+不是流体形成的推动力，但Na是 结合成阴离子或未解离的分子。我们将进行调查 如果这是真的，这个新概念应该会对离子研究产生深远的影响。 运输。 3.)我们继续研究我们的发现刘易斯或勃朗斯特德的质子化 酸可减少或消除房水分泌。这有理论上的原因 对分泌机制的影响，并提供了一种可能性 用新方法减少房水分泌物。在这方面，我们将 也要研究纤毛突起的pH值，以及酸对其的影响。 或者是碳酸酐酶抑制剂。 4.)我们将测量离子从等离子体到水的运动速度。 幽默，在服用各种已知的药物之前和之后 影响水的分泌，就像我们对碳酸酐酶所做的那样 抑制剂。这是眼科药理学中被忽视的一个方面；我们将 研究哇巴因、噻吗洛尔、匹罗卡品、肾上腺素和其他几种药物。是这样的 测量应该会揭示它们(目前尚不清楚)的机制。

The proposed work is divided into four related categories, all converging on the problems of aqueous humor formation and treatment of glaucoma: Development of new drugs (topical carbonic anhydrase inhibitors); study of ionic reactions underlying secretion of aqueous; exploration of the effect of A1C13 and other acids on aqueous secretion and pH of ciliary processes; effect of autonomic drugs and Na-K-ATPase inhibitors on electrolyte movement from plasma to aqueous. 1.) We are searching for a topical carbonic anhydrase inhibitor with properties such that 1 drop of solution will lower intraocular pressure in man for 6-12 hours. This demands a continuing effort in organic synthesis, analysis of physico-chemical properties of compounds, and aqueous humor dynamics in animals and man. Feasibility of this goal seems reasonable; it has already been achieved in the rabbit. Almost certainly, such a compound will have no systemic toxicity in man, or any other effect on the eye. 2.) We believe it possible (likely?) that in aqueous humor (and other secretory sites, as cerebrospinal fluid and pancreas), the observed linkage of Na+ and HCO3- has a specific chemical basis, in ion pairing of NaCO3- and NaHCO3-degrees. This has not been considered for epithelial secretion but has been entertained as a basis for HCO3- - Cl- exchange in red cells. In this view Na+ is not the moving force for fluid formation, but Na is incorporated into an anion or undissociated molecule. We shall investigate this; if true, the new concept should profoundly affect studies of ion transport. 3.) We continue to study our finding that protonation by Lewis or Bronsted acids reduces or abolishes aqueous humor secretion. This has theoretical implications for mechanisms of secretion and offers the possibility of reduction of aqueous secretion by new methods. In this context we shall also study the pH of ciliary process and how this may be changed by acids or by carbonic anhydrase inhibitors. 4.) We shall measure the rates of ion movement from plasma to aqueous humor, before and after administration of various classes of drugs known to affect aqueous secretion, as we have done with carbonic anhydrase inhibitors. This is a neglected aspect of ocular pharmacology; we shall study ouabain, timolol, pilocarpine, epinephrine, and several others. Such measurements should throw light on their (presently unknown) mechanism.