GLAUCOMA-NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼-新药和水液分泌机制
基本信息
- 批准号:3256606
- 负责人:
- 金额:$ 29.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1978
- 资助国家:美国
- 起止时间:1978-03-01 至 1995-02-28
- 项目状态:已结题
- 来源:
- 关键词:autonomic agents blood aqueous barrier carbonic anhydrase inhibitors cats choroid uvea dogs drug metabolism electrolyte balance enzyme inhibitors epinephrine eye pharmacology glaucoma intraocular fluid ion transport laboratory rabbit laboratory rat ocular hypotensive ouabain pilocarpine radioassay secretion sodium potassium exchanging ATPase sulfonamides
项目摘要
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.
拟议的工作分为四个相关的类别,
关于青光眼的形成和治疗的问题:
新药开发(局部碳酸酐酶抑制剂);
房水分泌的离子反应;效应的探讨
A1 C13和其他酸对睫状突的水分泌和pH的影响;
植物神经药物和Na-K-ATP酶抑制剂对电解质影响
从血浆到房水的移动。
1.)的人。我们正在寻找一种局部碳酸酐酶抑制剂,
特性,使得1滴溶液将降低眼内压,
男人6-12小时 这就要求在有机合成方面不断努力,
化合物和房水的理化性质分析
动物和人类的动力学。这个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,这种化合物
不会对人体产生全身毒性,也不会对眼睛产生任何影响。
2.)的情况。我们认为这是可能的(可能?)在房水(和其他
分泌部位,如脑脊液和胰腺),观察到的联系
Na+与HCO 3-的离子配对有特定的化学基础,
NaHCO 3-度。 这还没有被认为是上皮分泌
但一直被认为是红细胞中HCO 3- - Cl-交换的基础。
在这种观点中,Na+不是流体形成的推动力,但Na是
结合到阴离子或未解离的分子中。 我们会调查的
如果这是真的,这个新概念将深刻地影响离子的研究。
运输
3.)第三章我们继续研究刘易斯或布朗斯台德的质子化
酸减少或消除眼房水分泌。 这在理论上
分泌机制的影响,并提供了可能性,
通过新方法减少水分泌。 在这方面,我们将
我还研究了睫状突的pH值,以及它是如何被酸改变的
或通过碳酸酐酶抑制剂。
4.)我们将测量离子从等离子体到水溶液的运动速率
幽默,之前和之后的各种类型的药物管理已知,
影响水性分泌,正如我们对碳酸酐酶所做的那样
抑制剂的 这是一个被忽视的方面眼药理学;我们将
研究哇巴因、噻吗洛尔、毛果芸香碱、肾上腺素和其他几种药物。 等
测量结果应该能揭示其(目前未知的)机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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THOMAS H MAREN其他文献
THOMAS H MAREN的其他文献
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{{ truncateString('THOMAS H MAREN', 18)}}的其他基金
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256599 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256604 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256603 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256605 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
2158384 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
NEW PHARMACOLOGY ASPECTS RELATED TO CARBONIC ANHYDRASE
与碳酸酐酶相关的新药理学方面
- 批准号:
3336804 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256601 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256602 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
NEW PHARMACOLOGY ASPECTS RELATED TO CARBONIC ANHYDRASE
与碳酸酐酶相关的新药理学方面
- 批准号:
3336805 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
GLAUCOMA--NEW DRUGS AND MECHANISMS OF AQUEOUS SECRETION
青光眼--新药和水液分泌机制
- 批准号:
3256598 - 财政年份:1978
- 资助金额:
$ 29.78万 - 项目类别:
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