Effects of quinidine and verapamil on human cardiovascular α1- adrenoceptors

Abstract

Background: The antiarrhythmic drugs quinidine and verapamil are known to block α1-adrenoceptors (α1ARs). α1ARs 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 α1AR subtypes. Methods and Results: Reverse transcriptasepolymerase chain reaction showed that all α1AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the α1AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human α1AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all α1AR subtypes. Also, both drags synergistically inhibited α1AR-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 α1AR subtypes are expressed in the human cardiovascular system and that quinidine and verapamil may have a potent, synergistic inhibitory effect on the α1ARs. Clinically observed hypotension after quinidine plus verapamil can be explained by their synergistic inhibitory effects on human α1ARs.