α1-Adrenoceptor Blockade by Class I Antiarrhythmic Drugs in Guinea Pig Thoracic Aorta as Revealed by Mechanical and Fluorescence Displacement Analysis.

The effects of thirteen Vaughn Williams class I antiarrhythmic drugs on the α1-adrenergic receptor-mediated contraction were examined in thoracic aorta tissue preparations isolated from the guinea pig. Cibenzoline, quinidine, aprindine, and ranolazine, as well as prazosin, inhibited the phenylephrine-induced contraction with pA2 values of 5.64, 5.59, 5.61, 5.08, and 8.50, respectively, but not prostaglandin F2α-induced. These drugs reduced the staining of the smooth muscle layer by fluorescent prazosin. Propafenone inhibited the phenylephrine-induced contraction with an apparent pA2 value of 5.31 and reduced the staining by fluorescent prazosin, but also inhibited the prostaglandin F2α-induced contraction. Other class I antiarrhythmic drugs, disopyramide, pirmenol, procainamide, lidocaine, mexiletine, flecainide, pilsicainide, and GS-458967, affected neither the contraction by phenylephrine nor the fluorescent staining by prazosin. These results indicate that among the class I antiarrhythmic drugs, cibenzoline, aprindine, and propafenone, as well as quinidine and ranolazine, have α1-adrenoceptor-blocking activity at therapeutically relevant concentrations.