Biochem/physiol Actions
DPO-1 is an inhibitor of human Kv1.5 potassium channel; representative blocker of a novel pharmacophore. The Kv1.5 potassium channel, which underlies the ultrarapid delayed rectifier current, IKur, is reported to be enriched in human atrium versus ventricle, and has been proposed as a target for novel atrial antiarrhythmic therapy. The administration of the IKur blocker (2-isopropyl-5-methyl-cyclohexyl) diphenylphosphine oxide (DPO-1) increases myocardial refractoriness in both atrium and ventricle of rat, but produces an atrial-selective increase in refractoriness in primates; appears to be 15-fold more selective for Kv1.5 vs Kv3.1 channels expressed in Xenopus oocytes. IC50 = 0.16-0.76 μM at 0.1 Hz pulsing frequency; Kd = 0.6 μM. |
Biochem/physiol Actions
DPO-1 is an inhibitor of human Kv1.5 potassium channel; representative blocker of a novel pharmacophore. The Kv1.5 potassium channel, which underlies the ultrarapid delayed rectifier current, IKur, is reported to be enriched in human atrium versus ventricle, and has been proposed as a target for novel atrial antiarrhythmic therapy. The administration of the IKur blocker (2-isopropyl-5-methyl-cyclohexyl) diphenylphosphine oxide (DPO-1) increases myocardial refractoriness in both atrium and ventricle of rat, but produces an atrial-selective increase in refractoriness in primates; appears to be 15-fold more selective for Kv1.5 vs Kv3.1 channels expressed in Xenopus oocytes. IC50 = 0.16-0.76 μM at 0.1 Hz pulsing frequency; Kd = 0.6 μM. |