Delving into the Latest Updates on Bunazosin Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Andante, Bunazosin, Bunazosin hydrochloride (JP17)

+ [10]

Target

ADRA1

Action

antagonists

Mechanism

ADRA1 antagonists(Adrenergic receptor alpha-1 antagonists)

Therapeutic Areas

Cardiovascular DiseasesEye DiseasesUrogenital Diseases

Active Indication

GlaucomaHeart FailureHypertension+ [2]

Inactive Indication-

Originator Organization

Eisai Co., Ltd.

Active Organization

Eisai Co., Ltd.

Santen Pharmaceutical Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (16 Apr 1985),

Essential HypertensionHypertension, Renal

Regulation-

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Structure/Sequence

Molecular FormulaC19H27N5O3

InChIKeyRHLJLALHBZGAFM-UHFFFAOYSA-N

CAS Registry80755-51-7

View All Structures (2)

BACKGROUNDThere is no clear information on the regulation of liver blood flow by the autonomic nervous system. We conducted this study to investigate whether quiescent hepatic stellate cells (qHSCs) regulate liver blood flow in response to the sympathetic neurotransmitter norepinephrine (NE).METHODSqHSCs isolated from mice were cultured in Dulbecco's modified Eagle medium without fetal bovine serum for 1 day on collagen gel. NE-induced qHSC contraction was evaluated using the quantitative single-cell contraction measurement method that we had developed previously. For the measurement of liver perfusion pressure in situ, a buffer solution was perfused from the portal vein in mice.RESULTSNE-induced a reversible contraction of qHSCs. This contraction was suppressed by the nonmuscle myosin II inhibitor blebbistatin, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor H-1152, the calmodulin inhibitor W-7, the store-operated calcium channel inhibitor YM-58483, and the IP₃ receptor inhibitor xestospongin C. In contrast, the transient receptor potential C channel inhibitor SKF96365 did not affect the NE-induced contraction.CONCLUSIONThese results suggest that qHSCs contract in response to NE.NEW & NOTEWORTHYThe present study provides direct evidence for the first time that norepinephrine (NE) induces a reversible contraction of isolated single quiescent hepatic stellate cells (qHSCs) and further suggests that the NE-mediated qHSC contraction participates in the regulation of liver blood flow in vivo.

01 Apr 2024·Biomedicine & Pharmacotherapy

Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses

Article

Author: Wan, Yuzhou ; Gao, Mengqi ; Li, Yuxi ; Liu, Lin ; Chen, Kexu ; Rong, Jin ; Li, Xin ; Zhao, Tingting ; Wang, Shaopeng ; Yan, Meihua ; Dong, Xi ; Ma, Liang ; Li, Ping ; Qi, Huimin ; Zhang, Bo

BACKGROUNDTangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown.METHODWe conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body.RESULTSTSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota.CONCLUSIONTSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.

01 Mar 2024·Mitochondrion

DDQ anti-aging properties expressed with improved mitophagy in mutant tau HT22 neuronal cells

Article

Author: Rawat, Priyanka ; Reddy, Arubala P ; Pradeepkiran, Jangampalli Adi ; Orlov, Erika ; Reddy, P Hemachandra

The purpose of our study is to develop age-related phosphorylated tau (p-tau) inhibitors, for Alzheimer's disease (AD). There are wide-ranging therapeutic molecules available in the market and tested for age-related p-tau inhibition to enhance phosphatase activity and microtubule stability in AD neurons. Until now there are no such small molecules claimed to show promising results to delay the disease process of AD. However, a recently developed molecule, DDQ, has been shown to reduce abnormal protein-protein interactions and protect neurons from mutant protein-induced toxicities in the disease process. In addition, DDQ reduced age- and Aβ-induced oxidative stress, mitochondrial dysfunction, and synaptic toxicity. To date, there are no published reports on the p-tau interaction of DDQ and Sirt3 upregulation with CREB-mediated mitophagy activation in AD neurons. In the current study, HT22 cells were transfected with mutant Tau (mTau) cDNA and treated with the novel molecule DDQ. Cell survival, immunoblotting, and immunofluorescence analysis were conducted to assess cell viability and synaptic and mitophagy proteins in treated and untreated cell groups. As expected, we found cell survival was decreased in mTau-HT22 cells when compared with control HT22 cells. However, cell survival was increased in DDQ-treated mTau-HT22 cells when compared with mTau HT22 cells. P-tau and total tau proteins were significantly reduced in DDQ-treated mTau-HT22 cells, and MAP2 levels were increased. Anti-aging proteins like Sirt3, and CREB levels were increased in DDQ-treated HT22 cells and also in mTau-HT22 cells treated DDQ. Mitophagy proteins were decreased in mTau-HT22 cells and these were increased in DDQ-treated mTau-HT22 cells. These observations strongly suggest that DDQ has anti-p-tau and anti-aging properties, via Sirt3 overexpression and increased mitophagy proteins. Our study findings may have implications for healthy aging to the development of p-tau targeted therapeutics in AD and tauopathies.

100 Deals associated with Bunazosin Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D01887	Bunazosin Hydrochloride	C02	DB12230

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	Japan	Santen Pharmaceutical Co., Ltd.	20 Jun 2001
Heart Failure	Japan	Eisai Co., Ltd.	28 Feb 1995
Hypertension	Japan	Eisai Co., Ltd.	20 Jan 1995
Essential Hypertension	Japan	Eisai Co., Ltd.	16 Apr 1985
Hypertension, Renal	Japan	Eisai Co., Ltd.	16 Apr 1985

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2003	Not Applicable	-	-	Bunazosin Hydrochloride 0.01%	vvtkrcngbc(whkpprwlye) = xgrxnvopsl ornomrkodh (sbwhiccwbv )	Positive	01 May 2003
ARVO2002	Not Applicable	-	-	Nipradilol (1%)	(kisdcczekp) = hzmtmwlymc xdhloqjymk (ylfmxvfrks )	Positive	01 Dec 2002
ARVO2002	Not Applicable	-	-	Timolol (0.5%) and Bunazosin (0.125%)	(kisdcczekp) = xbdmewaeoy xdhloqjymk (ylfmxvfrks )	Positive	01 Dec 2002