The cardiac $\text{beta}$-adrenergic receptor blocking actions of propranolol and its stereoisomers

Abstract

The ability of propranolol and its dextrorotatory and levorotatory isomers to produce $\text{beta}$-adrenergic receptor blockade was studied in anesthetized dogs and in isolated rabbit atria. $\text{1}$-Propranolol, in mean concentrations of 3.8 × 10⁻⁷ M, and 4.9 × 10⁻⁷ M, produced a 50% attenuation of the positive inotropic and chronotropic effects, respectively, of isoproterenol on isolated rabbit atria. The corresponding mean concentrations of $\text{dl}$-Propranolol required were 7.4 × 10⁻⁷ M and 8.4 × 10⁻⁷ M. $\text{d}$-Propranolol failed to attenuate the responses to isoproterenol in concentrations 60–80 times higher than the required concentration of $\text{1}$-propranolol. In the anesthetized dog, $\text{dl}$-propranolol, 0.5 mg/kg, produced complete inhibition of the responses to isoproterenol and sympathetic stimulation. In contrast, no specific inhibition was observed following $\text{d}$-propranolol, 5 mg/kg. These findings provide additional support for the thesis that the stereochemical configuration of the sidechain alcoholic hydroxyl group is important in determining whether or not a drug of this class possesses affinity for the $\text{beta}$-adrenergic receptor; thus, allowing it to act as a $\text{beta}$-receptor blocking agent.