Effects of Quinidine and Verapamil on Human Cardiovascular α 1 -Adrenoceptors

Background —The antiarrhythmic drugs quinidine and verapamil are known to block α1 -adrenoceptors (α1 ARs). α1 ARs are a heterogeneous family of three subtypes (α1A , α1B , and α1D ), and little is known about the effects of quinidine and verapamil on the different human α1 AR subtypes.Methods and Results —Reverse transcriptase–polymerase chain reaction showed that all α1 AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the α1 AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human α1 AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all α1 AR subtypes. Also, both drugs synergistically inhibited α1 AR-mediated inositol 1,4,5-triphosphate production at the clinical effective concentration range (1 μmol/L quinidine and 0.1 μmol/L verapamil).Conclusions —The results show that all α1 AR subtypes are expressed in the human cardiovascular system and that quinidine and verapamil may have a potent, synergistic inhibitory effect on the α1 ARs. Clinically observed hypotension after quinidine plus verapamil can be explained by their synergistic inhibitory effects on human α1 ARs.