How the Deuteration of Dronedarone Can Modify Its Cardiovascular Profile: In Vivo Characterization of Electropharmacological Effects of Poyendarone, a Deuterated Analogue of Dronedarone.

How the Deuteration of Dronedarone Can Modify Its Cardiovascular Profile: In Vivo Characterization of Electropharmacological Effects of Poyendarone, a Deuterated Analogue of Dronedarone. Cardiovasc Toxicol. 2020 Jan 02;: Authors: Kambayashi R, Hagiwara-Nagasawa M, Kondo Y, Yeo ZJ, Goto A, Chiba K, Nunoi Y, Izumi-Nakaseko H, Leow JWH, Venkatesan G, Matsumoto A, Chan ECY, Sugiyama A Abstract Since deuterium replacement has a potential to modulate pharmacodynamics, pharmacokinetics and toxicity, we developed deuterated dronedarone; poyendarone, and assessed its cardiovascular effects. Poyendarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s was intravenously administered to the halothane-anesthetized dogs (n = 4), which provided peak plasma concentrations of 108 ± 10 and 1120 ± 285 ng/mL, respectively. The 0.3 mg/kg shortened the ventricular repolarization period. The 3 mg/kg transiently increased the heart rate at 5 min but decreased at 45 min, and elevated the total peripheral vascular resistance and left ventricular preload, whereas it reduced the mean blood pressure at 5 min, left ventricular contractility and cardiac output. The transient tachycardic action is considered to be induced by the hypotension-induced, reflex-mediated increase of sympathetic tone. The 3 mg/kg delayed both intra-atrial and intra-ventricular conductions, indicating Na+ channel inhibitory action. Moreover, the 3 mg/kg transient...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research