Since the discovery of Warfarin in the 1940s, the design of new warfarin-derived anticoagulants for rodent management has been challenging, with mainly structural modifications performed on the C3 position of the coumarin skeleton. In order to better understand the pharmacomodulation of such derivatives, we have synthesized a family of C3 (linear and branched) alkyl-4-hydroxycoumarins, which led to the identification of compounds 5e and 5f as potential short-term active anticoagulants.
View Article and Find Full Text PDFDifenacoum, an antivitamin K anticoagulant, has been widely used as rodenticide to manage populations of rodents. Difenacoum belongs to the second generation of anticoagulant, and, as all the molecules belonging to the second generation of anticoagulant, difenacoum is often involved in primary poisonings of domestic animals and secondary poisonings of wildlife by feeding contaminated rodents. To develop a new and ecofriendly difenacoum, we explored in this study the differences in properties between diastereomers of difenacoum.
View Article and Find Full Text PDFBackground: Antivitamin K anticoagulant (AVK) rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the VKORC1 enzyme essential for the recycling of vitamin K, and thus prevent blood clotting and cause death by haemorrhage. Numerous mutations or polymorphisms of the Vkorc1 gene were reported in rodents, and some led to resistance to rodenticides.
View Article and Find Full Text PDFVitamin K antagonists (VKA) are used either in human medicine to prevent thromboembolic disorders or as rodenticides for pest control management. In rodents, female rats are described to be more tolerant to the action of vitamin K antagonists than males. Nevertheless, the mechanism of this greatest tolerance is still unknown and this study aims to identify the origin of this greatest tolerance after VKA administration.
View Article and Find Full Text PDFTwo distinguishable chemotypes of Ferula communis have been described: the 'nonpoisonous' chemotype, containing as main constituents the daucane esters; and the 'poisonous' chemotype containing prenylated coumarins, such as ferulenol and ferprenin. Ferulenol and ferprenin are 4-oxygenated molecules such as dicoumarol and warfarin, the first developed antivitamin K molecules. Antivitamin K molecules specifically inhibit VKORC1, an enzyme essential for recycling vitamin K.
View Article and Find Full Text PDFThe systematic use of antivitamin K anticoagulants (AVK) as rodenticides caused the selection of rats resistant to AVKs. The resistance is mainly associated to genetic polymorphisms in the Vkorc1 gene encoding the VKORC1 enzyme responsible for the reduction of vitamin K 2,3-epoxide to vitamin K. Five major mutations, which are responsible for AVK resistance, have been described.
View Article and Find Full Text PDFIohexol plasma clearance as a measure of glomerular filtration was determined in 31 dogs and 19 cats after an intravenous (i.v.) bolus injection.
View Article and Find Full Text PDFThe purpose of this study was to evaluate simplified methods for iohexol plasma clearance estimation in dogs and cats. Serial blood samples were taken before and 5, 20, 40, 60, 80, 100, 120, 150, 180, and 240 minutes after a bolus injection of iohexol in 51 dogs and 25 cats. Iohexol plasma concentration was determined with X-ray fluorescence.
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