Delving into the Latest Updates on Nipradilol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Nipradilol (JAN/INN)

+ [3]

Target

β-adrenoceptors

Mechanism

β-adrenoceptors antagonists(Beta adrenergic receptors antagonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEye Diseases

Active Indication

GlaucomaAngina PectorisHypertension

Inactive Indication-

Originator Organization-

Active Organization

Teika Pharmaceutical Co., Ltd.

Kowa Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (20 Sep 1988),

Angina PectorisHypertension

Regulation-

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Structure

Molecular FormulaC15H22N2O6

InChIKeyOMCPLEZZPVJJIS-UHFFFAOYSA-N

CAS Registry81486-22-8

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.

01 Jan 2014·Retinal Degenerative DiseasesQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Dec 2012·Neurochemistry InternationalQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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 Deals associated with Nipradilol

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External Link

KEGG	Wiki	ATC	Drug Bank
D01691	Nipradilol	S01EA	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	JP	Teika Pharmaceutical Co., Ltd.	16 Jun 1996
Angina Pectoris	JP	Kowa Co., Ltd.	20 Sep 1988
Hypertension	JP	Kowa Co., Ltd.	20 Sep 1988

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2011	Not Applicable	-	8	Topical Nipradilol	(wonanzyqln) = hcfyoslqbf jgzsnjkgzw (yhsebfxrol ) View more	-	01 Apr 2011
ARVO2004	Not Applicable	Diabetic Retinopathy	-	Nipradilol-treated eyes	(vyvloopidm) = ngawaiaqly bqpeyhtjwq (aekvbfitor )	-	01 May 2004
				topical nipradilol	(vyvloopidm) = gjfawsqyzv bqpeyhtjwq (aekvbfitor )
ARVO2002	Not Applicable	-	-	Nipradilol (1%)	(tmrszqfvpj) = eobelbqsmm gimqwihvvw (pjjfraxjgz )	Positive	01 Dec 2002
				Timolol (0.5%) and Bunazosin (0.125%)	(tmrszqfvpj) = yagcwcpgra gimqwihvvw (pjjfraxjgz )