Aim: Mozavaptan is a nonpeptide vasopressin receptor antagonist approved for the treatment of ectopic antidiuretic hormone secretion syndrome.
Methods & Results: A simple, rapid and fully validated UPLC/MS-MS method was developed for the quantitation of mozavaptan in rat plasma. The chromatographic separation was conducted on an Acquity UPLC BEH™ C column with an optimum mobile phase of 10 mM ammonium acetate buffer and 0.1% formic acid in acetonitrile (30:70 v/v) at a flow rate of 0.3 ml/min. The multiple reaction monitoring transitions were performed at m/z 428.16→119.03 for mozavaptan and m/z 237.06→179.10 for carbamazepine (internal standard).
Conclusion: The method was effectively applied for the determination of mozavaptan pharmacokinetic parameters after the oral administration of 3 mg/kg mozavaptan in rats.
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http://dx.doi.org/10.4155/bio-2018-0092 | DOI Listing |
Am J Physiol Renal Physiol
June 2024
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
We have previously shown that kidney collecting ducts make vasopressin. However, the physiological role of collecting duct-derived vasopressin is uncertain. We hypothesized that collecting duct-derived vasopressin is required for the appropriate concentration of urine.
View Article and Find Full Text PDFToxicol Lett
January 2023
MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK. Electronic address:
Tolvaptan is an effective drug for the treatment of autosomal dominant polycystic kidney disease, but its use is associated with a significant risk of T-cell-mediated liver injury in a small number of patients. An important clinical conundrum following the contraindication of tolvaptan is whether administration of agents of similar pharmacological action and structure will be tolerated. Herein, we addressed this question through the exposure of tolvaptan-responsive T-cell clones to similar pharmaceutical agents.
View Article and Find Full Text PDFEur J Pharmacol
August 2020
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. Electronic address:
The vasopressin V receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target for water balance disorders such as polycystic kidney disease. Traditionally, the discovery of novel agents for the vasopressin V receptor has been guided by evaluating their receptor affinity, largely ignoring the binding kinetics. However, the latter is receiving increasing attention in the drug research community and has been proved to be a more complete descriptor of the dynamic process of ligand-receptor interaction.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
May 2020
Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine, Institute of Nautical Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China
It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling.
View Article and Find Full Text PDFSci Rep
April 2019
Department of Human Genetics, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Compounds that are candidates for drug repurposing can be ranked by leveraging knowledge available in the biomedical literature and databases. This knowledge, spread across a variety of sources, can be integrated within a knowledge graph, which thereby comprehensively describes known relationships between biomedical concepts, such as drugs, diseases, genes, etc. Our work uses the semantic information between drug and disease concepts as features, which are extracted from an existing knowledge graph that integrates 200 different biological knowledge sources.
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