尼普地洛(Nipradilol) - 药物靶点：β-adrenoceptors_在研适应症：青光眼，心绞痛，高血压_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Nipradilol (JAN/INN)

+ [3]

靶点

β-adrenoceptors

作用机制

β-adrenoceptors拮抗剂(β-肾上腺素能受体家族拮抗剂)

治疗领域

神经系统疾病心血管疾病眼部疾病

在研适应症

青光眼心绞痛高血压

非在研适应症-

原研机构-

在研机构

Teika Pharmaceutical Co., Ltd.

Kowa Co., Ltd.

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (1988-09-20),

心绞痛高血压

最高研发阶段(中国)-

特殊审评-

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结构

分子式C15H22N2O6

InChIKeyOMCPLEZZPVJJIS-UHFFFAOYSA-N

CAS号81486-22-8

关联

3

项与尼普地洛相关的临床试验

JPRN-UMIN000011778 / CompletedIIT

Therapeutic outcome of unoprostone and nipradilol in patients with normal tension glaucoma. - Therapeutic outcome of unoprostone and nipradilol

开始日期2011-07-01

申办/合作机构-

JPRN-UMIN000006820 / CompletedIIT

Neuroprotective efficacy of topical unoprostone isopropyl or nipradilol in patients with retinitis pigmentosa - Neuroprotective efficacy of topical unoprostone isopropyl or nipradilol in patients with retinitis pigmentosa

开始日期2009-02-01

申办/合作机构-

JPRN-C000000422 / Completed临床4期

Randomized double blind comparative study of nipradilol, an alfa-1,beta-blocker with a nitric oxide donative action, and timolol, a non-selective beta-blocker, on the visual field in Japanese patients with normal-tension glaucoma. - Japanese Normal Tension Glaucoma Treatment Study (JNTGTS)

开始日期2002-04-01

申办/合作机构

Kowa Co., Ltd.

100 项与尼普地洛相关的临床结果

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100 项与尼普地洛相关的转化医学

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100 项与尼普地洛相关的专利（医药）

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160

项与尼普地洛相关的文献（医药）

2017-01-01·Journal of Ophthalmology4区 · 医学

Additive Intraocular Pressure-Lowering Effects of Ripasudil with Glaucoma Therapeutic Agents in Rabbits and Monkeys

4区 · 医学

ArticleOA

作者: Mizuno, Ken ; Nakamura, Yuto ; Isobe, Tomoyuki ; Ohta, Masayuki ; Kaneko, Yoshio

Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP) by increasing conventional outflow through the trabeculae to Schlemm’s canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys. Ripasudil showed additional effects on maximum IOP lowering or prolonged the duration of IOP-lowering effects with combined administration of timolol, nipradilol, brimonidine, brinzolamide, latanoprost, latanoprost/timolol fixed combination, and dorzolamide/timolol fixed combination. These results indicate that facilitation of conventional outflow by ripasudil provides additive IOP-lowering effect with other classes of antiglaucoma agents. Ripasudil is expected to have substantial utility in combined regimens with existing agents for glaucoma treatment.

2014-01-01·Retinal Degenerative Diseases4区 · 医学

Nipradilol Promotes Axon Regeneration Through S-Nitrosylation of PTEN in Retinal Ganglion Cells

4区 · 医学

Article

作者: Kazuhiro Ogai ; Kunizo Arai ; Satoru Kato ; Marie Kamiya ; Kayo Sugitani ; Yoshiki Koriyama

Nipradilol (Nip) is registered as an anti-glaucoma agent. More recently, a protective effect of Nip has been demonstrated in retinal ganglion cells (RGCs) mediated by S-nitrosylation of antioxidative-related Keap1 protein due to its nitric oxide (NO)-donating effect. It also has been reported that Nip promoted axon outgrowth in cat RGCs. However, the detailed mechanism remains unclear. NO physiologically regulates numerous cellular responses through S-nitrosylation of protein at cysteine residues. It has been reported that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) deletion strongly showed axon regeneration after optic nerve injury. PTEN inactivation by S-nitrosylation results in the accumulation of phosphatidylinositol (3, 4, 5) triphosphate (PIP3) and the activation of Akt/mammalian target of rapamycin (mTOR) signaling. The ribosomal S6 kinase 1 (S6K) which can monitor as phospho-S6 (pS6) is one of major target of mTOR. In this study, we investigated the possibility that Nip can promote axon outgrowth in RGCs by Akt/mTOR signaling thorough S-nitrosylation of PTEN.

2012-12-01·Neurochemistry International3区 · 医学

Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells

3区 · 医学

Article

作者: Tsuneo Takadera ; Kunizo Arai ; Marie Kamiya ; Satoru Kato ; Kazuhiro Ogai ; Yoshiki Koriyama ; Kayo Sugitani

Nipradilol (Nip), which has α1- and β-adrenoceptor antagonist and nitric oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous agent in Japan. NO mediates cellular signaling pathways that regulate physiological functions. The major signaling mechanisms mediated by NO are cGMP-dependent signaling and protein S-nitrosylation-dependent signalings. Nip has been described as having neuroprotective effects through cGMP-dependent pathway in retinal ganglion cells (RGCs). However, the effect seems to be partial. On the other hand, whether Nip can prevent cell death through S-nitrosylation is not yet clarified. In this study, we therefore focused on the neuroprotective mechanism of Nip through S-nitrosylation. Nip showed a dramatic neuroprotective effect against oxidative stress-induced death of RGC-5 cells. However, denitro-nipradilol, which does not have NO-donating properties, was not protective against oxidative stress. Furthermore, an NO scavenger significantly reversed the protective action of Nip against oxidative stress. In addition, we demonstrated that α1- or β-adrenoceptor antagonists (prazosin or timolol) did not show any neuroprotective effect against oxidative stress in RGC-5 cells. We also demonstrated that Nip induced the expression of the NO-dependent antioxidant enzyme, heme oxygenase-1 (HO-1). S-nitrosylation of Kelch-like ECH-associated protein by Nip was shown to contribute to the translocation of NF-E2-related factor 2 to the nucleus, and triggered transcriptional activation of HO-1. Furthermore, RGC death and levels of 4-hydroxy-2-nonenal (4HNE) were increased after optic nerve injury in vivo. Pretreatment with Nip significantly suppressed RGC death and accumulation of 4HNE after injury through an HO-1 activity-dependent mechanism. These data demonstrate a novel neuroprotective action of Nip against oxidative stress-induced RGC death in vitro and in vivo.

100 项与尼普地洛相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01691	尼普地洛	S01EA	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
青光眼	日本	Teika Pharmaceutical Co., Ltd.	1996-06-16
心绞痛	日本	Kowa Co., Ltd.	1988-09-20
高血压	日本	Kowa Co., Ltd.	1988-09-20

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ARVO2011	N/A	-	8	Topical Nipradilol	(繭餘選觸製鏇鏇窪製窪) = 願顧餘鹹獵觸廠壓顧簾鬱鹽網築願製選鏇鹹蓋 (淵簾廠遞鏇壓餘夢壓構 ) 更多	-	2011-04-01
ARVO2004	N/A	糖尿病性视网膜病变	-	Nipradilol-treated eyes	(鏇蓋顧鏇齋醖顧鹹壓壓) = 廠艱範鏇壓願願顧願壓襯積廠鏇鑰淵壓鏇蓋淵 (簾鹹醖壓壓醖鏇憲簾遞 )	-	2004-05-01
				topical nipradilol	(鏇蓋顧鏇齋醖顧鹹壓壓) = 醖廠獵繭積憲繭顧簾獵襯積廠鏇鑰淵壓鏇蓋淵 (簾鹹醖壓壓醖鏇憲簾遞 )
ARVO2002	N/A	-	-	Nipradilol (1%)	(憲鑰觸襯選淵簾齋鏇範) = 醖願壓夢鹹夢窪鬱膚範範鏇觸蓋獵壓鑰顧齋醖 (憲築憲鬱鬱餘製淵網鏇 )	积极	2002-12-01
				Timolol (0.5%) and Bunazosin (0.125%)	(憲鑰觸襯選淵簾齋鏇範) = 鹹積膚憲積窪鹽遞窪製範鏇觸蓋獵壓鑰顧齋醖 (憲築憲鬱鬱餘製淵網鏇 )