Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in clinical trials for the treatment of hypertension, congestive heart failure and renal failure. In the present study, we tested various N-ethyl carbamate esters of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular-Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at 1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in plasma fenoldopam levels and renal blood flow. Administration of the 7,8-bis-N-ethyl carbamate ester of R-fenoldopam (SK&F R-106114) and the 4',7,8-tris-N-ethyl carbamate ester of R-fenoldopam (SK&F R-105058) at 1, 3 and 10 mumol/kg p.o. also resulted in dose-dependent increases in plasma fenoldopam levels and renal blood flow; however, both parameters remained elevated for at least 4 hr. Intravenous administration of SK&F R-105058 also resulted in sustained plasma fenoldopam levels and increases in renal blood flow, indicating that slow absorption was not the cause of the sustained effect. The present study indicates that N-ethyl carbamate esters of fenoldopam are fenoldopam prodrugs which result in sustained increases in renal blood flow and plasma fenoldopam levels.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease.
Kidney Int
December 2024
University Rouen Normandie, Institut national de la santé et de la recherche médicale (INSERM) U1096, Endothélium, Valvulopathies, Insuffisance cardiaque (EnVI), Rouen, France; Department of Pharmacology, Centre Hospitalier Universitaire (CHU) Rouen, Rouen, France; Centre d'Investigation CLinique-Centre de Ressources Biologiques (CIC-CRB) 1404, Rouen, France. Electronic address:
Article Synopsis
- The study explores how altered endothelial flow sensitivity related to polycystin deficiency contributes to hypertension in autosomal dominant polycystic kidney disease (ADPKD) patients.
- Nineteen ADPKD patients were treated with the dopamine receptor agonist rotigotine, showing that a higher dose significantly improved nitric oxide release and endothelial function without major changes in overall blood pressure.
- The findings suggest that targeting endothelial dopamine receptors could be a promising new treatment strategy to mitigate cardiovascular issues linked with ADPKD.
Application of a count data model to evaluate the anti-metastatic efficacy of QAP14 in 4T1 breast cancer allografts.
J Theor Biol
January 2023
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:
Dopamine D1 receptor (D1DR) is proved to be a promising target to prevent tumor metastasis, and our previous studies showed that QAP14, a potent anti-cancer agent, exerted inhibitory effect on lung metastasis via D1DR activation. Therefore, the purpose of the study was to establish count data models to quantitatively characterize the disease progression of lung metastasis and assess the anti-metastatic effect of QAP14. Data of metastatic progression were collected in 4T1 tumor-bearing mice.
View Article and Find Full Text PDFA positive-negative switching LC-MS/MS method for quantification of fenoldopam and its phase II metabolites: Applications to a pharmacokinetic study in rats.
J Chromatogr B Analyt Technol Biomed Life Sci
August 2021
Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA. Electronic address:
Fenoldopam is an approved drug used to treat hypotension. The purpose of this study is to develop and validate an LC-MS method to quantify fenoldopam and its major metabolites fenoldopam-glucuronide and fenoldopam-sulfate in plasma and apply the method to a pharmacokinetic study in rats. A Waters C column was used with 0.
View Article and Find Full Text PDFIn Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring.
Cell Physiol Biochem
June 2018
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.
Background/aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear.
View Article and Find Full Text PDFNEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)-Mediated Secretion of Aldosterone.
Hypertension
August 2017
From the Clinical Pharmacology Unit, Department of Medicine (C.M., S.G., J.Z.) and Medical Research Council Cancer Unit (T.I.J.), University of Cambridge, United Kingdom; Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, United Kingdom (W.Z.); Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom (M.G.); and the Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (J.Z., M.J.B.).
Heterogeneity among aldosterone-producing adenomas (APAs) has been highlighted by the discovery of somatic mutations. mutations predominate in large zona fasciculata (ZF)-like APAs; mutations in , , and are more likely to be found in small zona glomerulosa (ZG)-like APAs. Microarray comparison of mutant versus wild-type APAs revealed significant differences in transcriptomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!