Delving into the Latest Updates on Fenoldopam Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Fenoldopam, Fenoldopam mesylate (USP)

+ [8]

Target

ADRA2 x D1 receptor

Mechanism

ADRA2 agonists(Adrenergic receptors alpha-2 agonists), D1 receptor agonists(Dopamine D1 receptor agonists)

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Acute Kidney InjuryHeart DiseasesHypertension+ [2]

Originator Organization

Abbott Laboratories

Active Organization-

Inactive Organization

Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd.

Hospira, Inc.

Abbott Laboratories

Drug Highest PhaseWithdrawn

First Approval Date

US (23 Sep 1997),

Hypertension, Malignant

Regulation-

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Structure

Molecular FormulaC17H20ClNO6S

InChIKeyCVKUMNRCIJMVAR-UHFFFAOYSA-N

CAS Registry67227-57-0

View All Structures (2)

The investigators will conduct a prospective, blinded, randomized, placebo-controlled trial with a sample size of 20 patients in each of the two arms (fenoldopam vs placebo) based upon a difference in serum creatinine by one standard deviation. Fluid and salt intake will be held constant within clinical parameters and carefully measured. Fenoldopam will be started at 0.1 ug/kg/min. If, after 6 hrs there is no decrease in blood pressure, the dose will be increased to 0.2 ug/kg/min. This dose will be continued throughout the remainder of the study. A study of pediatric patients previously provided to the FDA showed no hypotension at a dose of 0.2 ug/kg/min. Fenoldopam will be started 12 hrs before the first dose of indomethacin and discontinued 12 hrs after the 3rd dose of indomethacin. Study samples will include both blood and urine. The primary outcome will be a reduction in renal dysfunction, as determined by creatinine and urine output over the course of treatment. Additional outcomes will include determination of known and novel metabolomic urine markers of renal dysfunction.

Start Date06 Feb 2019

Sponsor / Collaborator

Medical College of Wisconsin

CTR20131661 / CompletedPhase 1

甲磺酸非诺多泮注射液在高血压患者的人体药代动力学试验

[Translation] Pharmacokinetic study of fenoldopam mesylate injection in patients with hypertension

以高血压患者舒张压降低值来评价药物的线性关系，估算非诺多泮主要药代动力学参数。

[Translation]

The linear relationship of the drug was evaluated by the reduction of diastolic blood pressure in hypertensive patients, and the main pharmacokinetic parameters of fenoldopam were estimated.

Start Date05 Nov 2013

Sponsor / Collaborator

Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd.

CTR20130438 / CompletedPhase 2

甲磺酸非诺多泮注射液治疗高血压急症的随机、单盲、阳性药平行对照、多中心临床试验

[Translation] A randomized, single-blind, positive-drug parallel-controlled, multicenter clinical trial of fenoldopam mesylate injection in the treatment of hypertensive emergencies

以注射用硝普钠为对照，评价甲磺酸非诺多泮注射液治疗高血压急症的有效性和安全性。

[Translation]

To evaluate the efficacy and safety of fenoldopam mesylate injection in the treatment of hypertensive emergencies using sodium nitroprusside injection as a control.

Start Date04 Sep 2012

Sponsor / Collaborator

Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd.

100 Clinical Results associated with Fenoldopam Mesylate

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100 Translational Medicine associated with Fenoldopam Mesylate

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100 Patents (Medical) associated with Fenoldopam Mesylate

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796

Literatures (Medical) associated with Fenoldopam Mesylate

12 Aug 2024·Journal of Biomolecular Structure and Dynamics

Computational screening and MM/GBSA-based MD simulation studies reveal the high binding potential of FDA-approved drugs against Cutibacterium acnes sialidase

Article

Author: Raza, Khalid ; Gautam, Hemant K ; Ahmad, Shaban ; Singh, Akash Pratap

Cutibacterium acnes is an opportunistic pathogen linked with acne vulgaris, affecting 80-90% of teenagers globally. On the leukocyte (WBCs) cell surface, the cell wall anchored sialidase in C. acnes virulence factor, catalysing the sialoconjugates into sialic acids and nutrients for C. acnes resulting in human skin inflammation. The clinical use of antibiotics for acne treatments has severe adverse effects, including microbial dysbiosis and resistance. Therefore, identifying inhibitors for primary virulence factors (Sialidase) was done using molecular docking of 1030 FDA-approved drugs. Initially, based on binding energies (ΔG), Naloxone (ZINC000000389747), Fenoldopam (ZINC000022116608), Labetalol (ZINC000000403010) and Thalitone (ZINC000000057255) were identified that showed high binding energies as -10.2, -10.1, -9.9 and -9.8 kcal/mol, respectively. In 2D analysis, these drugs also showed considerable structural conformer of hydrogen and hydrophobic interactions. Further, a 100 ns MD simulation study found the lowest deviation and fluctuations with various intermolecular interactions to stabilise the complexes. Out of 4, the Naloxone molecule showed robust, steady, and stable RMSD 0.23 ± 0.18 nm. Further, MMGBSA analysis supports MD results and found strong binding energy (ΔG) -29.71 ± 4.97 kcal/mol. In Comparative studies with Neu5Ac2en (native substrate) revealed naloxone has a higher affinity for sialidase. The PCA analysis showed that Naloxone and Thalitone were actively located on the active site, and other compounds were flickered. Our extensive computational and statistical report demonstrates that these FDA drugs can be validated as potential sialidase inhibitors.Communicated by Ramaswamy H. Sarma.

01 Aug 2024·Kidney International

Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease

Article

Author: Duflot, Thomas ; Enzensperger, Christoph ; Renet, Sylvanie ; Remy-Jouet, Isabelle ; Iacob, Michèle ; Hamzaoui, Mouad ; Bellien, Jérémy ; Dumont, Audrey ; Lévêque, Emilie ; Bertrand, Dominique ; Audrézet, Marie-Pierre ; Richard, Vincent ; Groussard, Déborah ; Brunel, Valéry ; Guerrot, Dominique ; Le Roy, Frank ; Arndt, Hans-Dieter ; Chevalier, Laurence ; Michel-Després, Aurore ; Hanoy, Mélanie ; Joannidès, Robinson ; Dumesnil, Anaïs

Altered polycystin-mediated endothelial flow mechanosensitivity contributes to the development of hypertension and cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD). Stimulation of endothelial type 5 dopamine receptors (DR5) can acutely compensate for the endothelial consequences of polycystin deficiency, but the chronic impact of this approach must be evaluated in ADPKD. Nineteen patients with ADPKD on standard of care therapy were randomized to receive a 2-month treatment with the DR agonist rotigotine using transdermal patches, nine at 2 mg/24hours and ten at 4 mg/24hours or while ten were untreated. Rotigotine at the dose of 4 mg/24hours significantly increased nitric oxide release (nitrite levels from 10±30 to 46±34 nmol/L) and radial artery endothelium-dependent flow-mediated dilatation (from 16.4±6.3 to 22.5±7.3%) in response to hand skin heating. Systemic hemodynamics were not significantly modified but aplanation tonometry showed that rotigotine at 4 mg/24hours reduced aortic augmentation index and pulse pressure without affecting carotid-to femoral pulse wave velocity. Plasma creatinine and urea, urinary cyclic AMP, which contributes to cyst growth in ADPKD and copeptin, a surrogate marker of vasopressin, were not affected by rotigotine. In mice with a specific deletion of polycystin-1 in endothelial cells, chronic infusion of the peripheral DR5 agonist fenoldopam also improved mesenteric artery flow-mediated dilatation and reduced blood pressure. Thus, our study demonstrates that in patients with ADPKD, chronic administration of rotigotine improves conduit artery endothelial function through the restoration of flow-induced nitric oxide release as well as hemodynamics suggesting that endothelial DR5 activation may represent a promising pharmacological approach to prevent cardiovascular complications of ADPKD.

01 Jan 2024·Cells Tissues Organs

Osteoclastogenesis Requires Primary Cilia Disassembly and Can Be Inhibited by Promoting Primary Cilia Formation Pharmacologically

Article

Author: Sutton, Michael M ; Jacobs, Christopher R ; Verbruggen, Stefaan W ; Duffy, Michael P

The primary cilium is a solitary, sensory organelle with many roles in bone development, maintenance, and function. In the osteogenic cell lineage, including skeletal stem cells, osteoblasts, and osteocytes, the primary cilium plays a vital role in the regulation of bone formation, and this has made it a promising pharmaceutical target to maintain bone health. While the role of the primary cilium in the osteogenic cell lineage has been increasingly characterized, little is known about the potential impact of targeting the cilium in relation to osteoclasts, a hematopoietic cell responsible for bone resorption. The objective of this study was to determine whether osteoclasts have a primary cilium and to investigate whether or not the primary cilium of macrophages, osteoclast precursors, serves a functional role in osteoclast formation. Using immunocytochemistry, we showed the macrophages have a primary cilium, while osteoclasts lack this organelle. Furthermore, we increased macrophage primary cilia incidence and length using fenoldopam mesylate and found that cells undergoing such treatment showed a significant decrease in the expression of osteoclast markers tartrate-resistant acid phosphatase, cathepsin K, and c-Fos, as well as decreased osteoclast formation. This work is the first to show that macrophage primary cilia resorption may be a necessary step for osteoclast differentiation. Since primary cilia and preosteoclasts are responsive to fluid flow, we applied fluid flow at magnitudes present in the bone marrow to differentiating cells and found that osteoclastic gene expression by macrophages was not affected by fluid flow mechanical stimulation, suggesting that the role of the primary cilium in osteoclastogenesis is not a mechanosensory one. The primary cilium has been suggested to play a role in bone formation, and our findings indicate that it may also present a means to regulate bone resorption, presenting a dual benefit of developing ciliary-targeted pharmaceuticals for bone disease.

100 Deals associated with Fenoldopam Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
D00613	Fenoldopam Mesylate	C01CA19	DB00800

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	CN	Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd.	04 Sep 2012
Acute Kidney Injury	Phase 2	-	Abbott Laboratories	01 May 2002
Heart Diseases	Phase 2	-	Abbott Laboratories	01 May 2002
Kidney Failure, Chronic	Phase 2	-	Abbott Laboratories	01 May 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02620761 (Fenaki, CTgov)	Phase 2/3	Ductus Arteriosus, Patent \| Acute Kidney Injury	1	0.9%NS (Control)	wvccdcqqqs(yzgnmtscvd) = dzvpbzxywu dwerzfqnyd (ytmepbaycn, yqukidjwup - gmxemghwqz) View more	-	16 Sep 2022
				Fenoldopam (Fenoldopam)	wvccdcqqqs(yzgnmtscvd) = mphnbkdxsc dwerzfqnyd (ytmepbaycn, ufvesokltv - udwjewafbn) View more
NCT00743106 (CTgov)	Not Applicable	Nephrosis	90	Placebo (Placebo)	gvcmxdgfph(nbhlregvpe) = yqmcbehjgw lycflxqghh (bkopubkenf, yfzqioveep - mnqchkepvv) View more	-	31 Oct 2016
				Fenoldopam (Fenoldopam)	gvcmxdgfph(nbhlregvpe) = ynmokjlihv lycflxqghh (bkopubkenf, uqeawkecur - cefhciwibj) View more
NCT00621790 (Pubmed \| J Coll Physicians Surg Pak)	Phase 3	Acute Kidney Injury	667	Fenoldopam	(vquesnpulq) = kbjrkhxbfu srysnwhwkm (ftiffcwbxs )	-	03 Dec 2014
				Placebo	(vquesnpulq) = qnhpylpllf srysnwhwkm (ftiffcwbxs )