Effects of Bunitrolol on Adrenergic and Serotonergic Receptors

To assess the importance of anti-adrenergic and anti-serotonergic activities of bunitrolol for its efficacy as an antihypertensive and antianginal agent, effects of this substance on the binding of adrenergic and serotonergic agents to the respective receptors of the rat brain, rat heart, dog brain, and/or dog aorta were examined using the radioligand binding assay methods. In addition, the pA2 values of bunitrolol as an antagonist against the positive chronotropic and inotropic actions (β1-adrenoceptor) of isoproterenol were also determined by pharmacological methods using the isolated guinea pig atria. To assess the specificity, pA2 values were also obtained in the isolated trachea (β2-adrenoceptor) using isoproterenol as an agonist and in the isolated aorta from the guinea pig and the rat using phenylephrine as an agonist (α1-adrenoceptor). A strong inhibition by bunitrolol of 3H-dihydroalprenolol (3H-DHA) binding to β-adrenoceptors was observed, while the inhibition of 3H-prazosin binding to α1-adrenoceptors, 3H-serotonin binding to 5HT1-receptors. 3H-p-aminoclonidine binding to α2-adrenoceptors, and 3H-ketanserin binding to 5HT2-receptors were found to be very weak. The rank order of antagonistic potencies of bunitrolol against the adrenergic receptors as asessed with pA2 values were β1>β2>>α1. From these two different types of experiments, it is clear that the antihypertensive and antianginal effects of bunitrolol are mainly due to its β-blocking actions, with the α1-blocking action of this drug playing a minor role.