fenoldopam / Generic mfg. - LARVOL DELTA

Renal Neuropeptide FF Receptor 2, via the Stress Response Element Within Its Gene Promoter Region and Interaction with Dopamine D1 Receptor and Angiotensin II Type 1 Receptor, Regulates Blood Pressure (KIDNEY WEEK 2025) - "In human RPTCs, NPFFR2 colocalized and co-immunoprecipitated with D 1 R. Fenoldopam (Fen, 1 µM), a D 1 R agonist, impaired Na + transport from inside to outside the cell, shown by increased intracellular Na + concentration, detected by the increase in lifetime t 2 measured by FLIM...In kidneys, NPFFR2 also colocalized with AT 1 R, and NPFFR2 co-immunoprecipitated with AT 1 R. The renal subcapsular infusion of NPFF (10 µg in 100 µL) for 7 days increased the systolic BP, which was attenuated by the femoral vein infusion of Fen (2 µg/kg/min) by osmotic minipump, whereas, systolic BP was individually and synergistically increased by renal subcapsular infusion of NPFF (10 µg/100 µL) and Ang II (20 µg/100 µL) 0.5 µL/hr for 7 days. Conclusion Renal NPFFR2 regulates BP through SRE within its promotor and its interaction with D 1 R and AT 1 R in the kidney."

Anesthesia

Non-catalytic UBL2 domain directs deubiquitinase USP11 toward K48-linked polyubiquitin chains. (PubMed, J Biol Chem) - "By leveraging AI-based virtual screening, we have identified selective USP11 inhibitors, including the FDA-approved drugs Fenoldopam and Olanzapine and their analogs, which act through a unique chemical scaffold and display significant efficacy both in vitro and in cells. Our findings not only uncover a previously unrecognized mechanism of linkage selectivity within the USP family but also provide a robust platform for the rational design of USP11-targeted therapeutics, underscoring the critical role of non-catalytic domains in deubiquitinase regulation and offering promising avenues for therapeutic intervention."

Journal • CNS Disorders • Oncology • Targeted Protein Degradation • USP11 • USP4

Case Report: Bevacizumab-induced renal-limited TMA and FSGS-like lesions in a kidney transplant recipient. (PubMed, Front Oncol) - "We present a case of nephrotic syndrome and renal insufficiency arising from small intestinal mucinous adenocarcinoma 17 years post-renal transplantation, treated with bevacizumab and sindilizumab. Upon discontinuation of the antitumor drugs and initiation of treatment with telmisartan, fenoldopam, and ambrisentan, proteinuria markedly decreased and eGFR improved. No tumor recurrence was observed over a follow-up period exceeding six months."

Journal • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Oncology • Renal Disease • Transplantation

Integrative genetic analysis of shared genetic architecture of stroke and coronary artery disease: implications for pharmacist-led precision medicine. (PubMed, Int J Clin Pharm) - "This study provides genomic evidence to support integrated therapeutic strategies for stroke and CAD. Pharmacogenomic insights into shared genetic determinants can assist clinical pharmacists in optimizing treatment selection, mitigating polypharmacy risks, and guiding precision medicine in patients with dual cardiocerebrovascular risks."

Journal • Cardiovascular • Coronary Artery Disease

Fenoldopam use during Cardiopulmonary Bypass and Postoperative Rates of Acute Kidney Injury. (PubMed, P R Health Sci J) - "While the administration of fenoldopam prior to CPB in patients with CKD stage 3 or higher did not significantly reduce AKI after cardiac surgery or significantly reduce length of stay, possible renal protective properties were identified. Being female and having an adequate preoperative hematocrit level were identified as possible investigative points for future studies."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate D1R Endocytosis and Signaling. (PubMed, Biomedicines) - "In mouse RPTCs transfected with wild-type (WT) Snx19, fenoldopam (FEN), a D1-like receptor agonist, increased the colocalization of SNX19 with caveolin-1 and flotillin-1. FEN also increased the co-immunoprecipitation of SNX19 with caveolin-1 and flotillin-1, effects that were prevented by SCH39166, a D1-like receptor antagonist...Nocodazole, a microtubule depolymerization inhibitor, interfered with the FEN-mediated increase in the colocalization between SNX19 and D1R. SNX19 contains caveolin-1 and flotillin-1 binding motifs, which play an important role in D1R endocytosis and signaling."

Journal • CAV1 • FLOT1 • SNX

Unlocking the secrets of trace amine-associated receptor 1 agonists: new horizon in neuropsychiatric treatment. (PubMed, Front Psychiatry) - "Recent cryogenic electron microscopic (cryo-EM) structures of human and mouse TAAR1 (hTAAR1 and mTAAR1, respectively) in complex with agonists and G proteins have revealed detailed atomic insights into the binding pockets, binding interactions and binding modes of several agonists including endogenous trace amines (β-phenylethylamine, 3-Iodothyronamine), psychostimulants (amphetamine, methamphetamine), clinical compounds (ulotaront, ralmitaront) and repurposed drugs (fenoldopam). The in vitro screening of drug libraries has also led to the discovery of novel TAAR1 agonists (asenapine, guanabenz, guanfacine) which can be used in clinical trials or further developed to treat different neuropsychiatric conditions...In this review, we discuss the emergence of structure-based approaches in the discovery of novel TAAR1 agonists through drug repurposing strategies and structure-guided designs. Additionally, we discuss the functional selectivity of TAAR1 signalling, which..."

Journal • Review • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Fenoldopam for preventing and treating acute kidney injury. (PubMed, Cochrane Database Syst Rev) - "Fenoldopam administration in patients at risk of AKI is probably associated with a lower risk of developing AKI and shorter ICU stay when compared with placebo or saline, but has little or no effect on the need for KRT or the risk of death. In those undergoing cardiac surgery, fenoldopam may not confer any benefits compared with placebo or saline. Furthermore, it remains unclear whether fenoldopam is more or less effective than either dopamine or NAC in reducing the risk for AKI or the need for KRT. Further well-designed and adequately powered studies are required to evaluate the efficacy and safety of fenoldopam in preventing or treating AKI."

Clinical • Journal • Review • Acute Kidney Injury • Cardiovascular • Hypotension • Infectious Disease • Myocardial Infarction • Nephrology • Renal Disease • Septic Shock • Transplantation

SNX19 and p27 kip1 Regulate D1R Endocytosis in Renal Proximal Tubule Cells (KIDNEY WEEK 2024) - "Fenoldopam (FEN, 25 nM, 30 mins, n=3), a D1R/D5R agonist, increased their co-immunoprecipitation... SNX19 in the RPT interacts with p27Kip1 in the lipid rafts to regulate SNX19-mediated D1R endocytosis and subsequently, blood pressure."

Hypertension • CAV1 • FLOT1 • SNX

Fenoldopam for Renal Protection in Cardiac Surgery: Pharmacology, Clinical Applications, and Evolving Perspectives. (PubMed, J Clin Med) - "It also compares Fenoldopam to other renoprotective strategies, including dopamine, diuretics, and N-acetylcysteine. The review concludes by outlining future research directions and potential new applications of Fenoldopam in cardiac surgery. By providing a thorough overview of the current state of knowledge, this review aims to facilitate informed decision-making for clinicians and researchers while highlighting areas for future investigation."

Journal • Review • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury

Efficacy and safety of fenoldopam for the treatment of hypertensive crises in children with kidney disease: a retrospective study. (PubMed, Pediatr Nephrol) - "Fenoldopam seems effective and safe for the treatment of hypertensive crises in children with kidney disease, at a starting dose of 0.2 mcg/kg/min. Strict BP monitoring is required to identify possible excessive drop pressure in the first hours of infusion."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Critical care • Hypertension • Hypotension • Nephrology • Pediatrics • Renal Disease

Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease. (PubMed, Kidney Int) - "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."

Journal • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Genetic Disorders • Hypertension • Nephrology • Polycystic Kidney Disease • Renal Disease • PKD1

Contractile effects of stimulation of D1-dopamine receptors in the isolated human atrium. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Moreover, contractile effects of dopamine in the presence of propranolol 0.4 µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH 23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP."

Journal

Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure. (PubMed, Sci Rep) - "The increase in cAMP production in human RPTCs caused by fenoldopam, a D1-like receptor agonist, was attenuated by NPFF, indicating an antagonistic interaction between NPFF and D1-like receptors...The NPFF-mediated increase in blood pressure was prevented by RF-9, an antagonist of NPFF receptors. Taken together, our findings suggest that autocrine NPFF and its receptors in the kidney regulate blood pressure, but the mechanisms remain to be determined."

Journal • Cardiovascular • Hypertension

Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies. (PubMed, Molecules) - "This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information..."

Journal • Review • Breast Cancer • Cardiovascular • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Liver Cancer • Oncology • Solid Tumor

Nitroprusside-Induced Cyanide Toxicity in an Infant With Complex Congenital Cardiac Disease (SCCM 2024) - "To maximize systemic perfusion with a target ECMO flow of 100ml/kg/min, blood pressure (BP) control was attempted using SNP and fenoldopam infusions while other agents were avoided due to ongoing poor myocardial function...Due to concern for cyanide toxicity, SNP infusion was discontinued and the patient was treated empirically with hydroxocobalamin (70mg/kg)...Labs later resulted showing a cyanide level of 5.9mg/L (normal < 0.1mg/L) and a thiocyanate level of 23.0mcg/ml (normal < 4.0mcg/ml). This case illustrates the importance of vigilant monitoring of cyanide and thiocyanate levels for patients receiving SNP infusion for BP control, particularly while attempting to maximize ECMO flow in the post-resuscitation period when hepatic and renal dysfunction may be evolving."

Critical care • Heart Failure • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Dopamine Receptor 1 Impedes ILC2-Mediated Antitumor Immunity. (PubMed, J Immunol) - "Furthermore, fenoldopam, a selective DRD1 agonist, restrains the ILC2 response in the TME and aggravates tumor burden in mice. Taken together, our data elaborate that the DRD1 signal acts as an excitatory rheostat in regulating ILC2-dependent antitumor immunity."

Journal • Allergy • Immunology • Oncology • CD8

Modern and Non-Invasive Methods of Fat Removal. (PubMed, Medicina (Kaunas)) - "Moreover, there is potential in adenosine analogs, fenoldopam, rhubarb, the herbal extract Ephedra sinica Stapf, electroacupuncture simulation, and the drug CBL-514. Despite knowledge and experience, the ideal method for a quick and noticeable, but safe and non-invasive reduction of body fat has not been found yet. The research conducted nowadays may bring us closer to the development of a universal method, and turn out to be a breakthrough in the fight against overweight and obesity."

Journal • Aesthetic Medicine • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • IL6

Exercise Ameliorates Skeletal Muscle Insulin Resistance by modulating GRK4-mediated D1R expression. (PubMed, Clin Sci (Lond)) - "Previous studies showed dopamine D1-like receptor agonists, e.g., fenoldopam, could improve peripheral insulin sensitivity and antipsychotics which are dopamine receptor antagonists increased the susceptibility to type 2 diabetes (T2DM)...We found that the D1-like receptor antagonist, SCH23390, reduced the effect of exercise on lowering blood glucose and insulin in insulin-resistant mice, and inhibited the contraction-induced glucose uptake in C2C12 myotubes...Mechanistically, the upregulation of GRK4 expression caused by increased reactive oxygen species (ROS) in IR was ascribed to the enhanced expression of c-Myc, a transcriptional factor of GRK4. Taken together, this study shows that exercise, via regulation of ROS/c-Myc/GRK4 pathway, ameliorates D1R dysfunction and improves insulin sensitivity."

Journal • CNS Disorders • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • MYC

Computational screening and MM/GBSA-based MD simulation studies reveal the high binding potential of FDA-approved drugs against Cutibacterium acnes sialidase. (PubMed, J Biomol Struct Dyn) - "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. 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."

FDA event • Journal • Acne Vulgaris • Dermatitis • Dermatology • Inflammation

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients. (PubMed, Gynecol Oncol) - "DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC."

Journal • Endometrial Cancer • Oncology • Solid Tumor • ADRB2 • DRD1 • DRD2

Osteoclastogenesis requires primary cilia disassembly and can be inhibited by promoting primary cilia formation pharmacologically. (PubMed, Cells Tissues Organs) - "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...Since primary cilia and pre-osteoclasts 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."

Journal • Orthopedics • CTSK • FOS • TRAP

"Mercurial agents, triamterene and urea were also discussed. Other potential additions: aminophylline/theophylline, dopamine/fenoldopam…" (@VelezNephHepato)

Beneficial Impacts of Fenoldopam on Patients With or at Risk for Acute Renal Failure and Undergoing Surgery: A Meta-Analysis of Randomized Clinical Trials. (PubMed, Cureus) - "No significant differences were reported in terms of all-cause mortality, change in serum creatinine, and RRT. In conclusion, our meta-analysis of studies on the use of fenoldopam in adult patients undergoing major surgery showed that fenoldopam significantly reduces the risk of AKI and shortens ICU stays. However, there was no significant impact on all-cause mortality or RRT."

Clinical • Journal • Retrospective data • Review • Surgery • Acute Kidney Injury • Nephrology • Renal Disease

Dopamine Receptors in Breast Cancer: Prevalence, Signaling, and Therapeutic Applications. (PubMed, Crit Rev Oncog) - "Fenoldopam, which is FDA-approved to treat renal hypertension, could be repurposed as an effective therapeutic agent for patients with D1R-expressing tumors. Several drugs that interfere with the cGMP/PKG pathway and are approved for treating other diseases should also be considered as potential treatments for BC."

Journal • Breast Cancer • Cardiovascular • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hypertension • Oncology • Solid Tumor • ER • HER-2