2006) In vivo cardiac electrophysiologic effects of a novel diphenylphosphine oxide IKur blocker, (2-isopropyl5-methylcyclohexyl) diphenylphosphine oxide, in rat and nonhuman

The voltage-gated potassium channel, Kv1.5, which underlies the ultrarapid delayed rectifier current, IKur, is reported to be enriched in human atrium versus ventricle, and has been pro-posed as a target for novel atrial antiarrhythmic therapy. The administration of the novel IKur blocker (2-isopropyl-5-methyl-cyclohexyl) diphenylphosphine oxide (DPO-1) (0.06, 0.2, and 0.6 mg/kg/min i.v. 20 min; total doses 1.2, 4.0, and 12.0 mg/kg, respectively) to rat, which exhibits IKur in both atria and ventricle, elicited significant, dose-dependent increases in atrial and ventricular refractory period (9–42%) at all doses tested, with no changes in cardiac rate or indices of cardiac conduc-tion. Plasma levels achieved in rat at the end of the three infusions were 1.1, 4.1, and 7.7 M. Reverse transcription-polymerase chain reaction analysis of African green monke