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高眼压症的新型潜在治疗方式:聚焦于血管紧张素和缓激肽系统轴

Novel potential treatment modalities for ocular hypertension: focus on angiotensin and bradykinin system axes.

作者信息

Sharif Najam A

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University , Houston, Texas.

出版信息

J Ocul Pharmacol Ther. 2015 Apr;31(3):131-45. doi: 10.1089/jop.2014.0114. Epub 2015 Jan 19.

Abstract

Despite the availability of modern surgical procedures, new drug delivery techniques, health authority-approved single topical ocular drugs, and combination products thereof, there continues to be an unmet medical need for novel treatment modalities for preserving vision. This is especially true for the treatment of glaucoma and the high risk factor often associated with this ocular disease, elevated intraocular pressure (IOP). Undesirable local or systemic side effects, frequency of dosing, lack of sustained IOP lowering, and lack of prevention of diurnal IOP spikes are among the greatest challenges. The very recent discovery, characterization, and publication of 2 novel IOP-lowering agents that pertain to the renin-angiotensin and kallikrein-kinin axes potentially offer novel means to treat and control ocular hypertension (OHT). Here, some contextual introductory information is provided first, followed by more detailed discussion of the properties and actions of diminazene aceturate (DIZE; a novel angiotensin-converting enzyme-2 activator) and FR-190997 (a nonpeptide bradykinin receptor-2 agonist) in relation to their anti-OHT activities in rodent and cynomolgus monkey eyes, respectively. It is anticipated that these compounds will pave the way for future discovery, development, and marketing of novel drugs to treat glaucoma and thus help save sight for millions of people afflicted with this slow progressive optic neuropathy.

摘要

尽管有现代外科手术、新的药物递送技术、卫生当局批准的单一局部眼用药物及其联合产品,但对于保护视力的新型治疗方式仍存在未满足的医疗需求。对于青光眼的治疗以及与这种眼病常相关的高风险因素——眼压升高(IOP)而言尤其如此。不良的局部或全身副作用、给药频率、眼压持续降低不足以及昼夜眼压峰值缺乏预防是最大的挑战之一。最近发现、表征并发表的两种与肾素 - 血管紧张素和激肽释放酶 - 激肽轴相关的新型降眼压药物,可能为治疗和控制高眼压症(OHT)提供新方法。在此,首先提供一些背景介绍信息,随后更详细地讨论乙酰氧苯脒(DIZE;一种新型血管紧张素转换酶 - 2激活剂)和FR - 190997(一种非肽类缓激肽受体 - 2激动剂)的特性和作用,它们分别在啮齿动物和食蟹猴眼中具有抗高眼压症活性。预计这些化合物将为未来治疗青光眼的新药的发现、开发和上市铺平道路,从而帮助数百万患有这种缓慢进展性视神经病变的人挽救视力。

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