«2"Adrenergic Receptors

Although quinidine is known to have antiadrenergic effects in the cardiovascular system, the precise mechanism by which it exerts these effects is not well defined. We asked whether quinidine binds directly to adrenergic receptors. Radioligand-binding assays were used to identify <*i -adrenergic receptors ([H]prazosin-binding sites) on membranes prepared from rat heart and kidney, a2-adrenergic receptor ([ H]yohimbine-binding sites) on human platelets and rat kidney membranes, and /3-adrenergic receptors ([I]iodocyanopindolol-binding sites) on rat heart and kidney membranes. Although it did not effectively compete for binding to /3-adrenergic receptors, quinidine competed for binding to <*iand a2-adrenergic receptors and yielded equilibrium dissociation constants of 0.3-3 /*M. TWO other antiarrhythmic agents, lidocaine and procainamide, did not compete for binding to a-adrenergic receptors. Further experiments demonstrated that the interactions of quinidine with the cardiac c*iand platelet a2-adrenergic receptors were competitive and reversible. We conclude that that antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of «iand a2-adrenergic receptors. (Circ Res 55: 376-381, 1984)