Pharmacology of dl-5-methyl-8-(2-hydroxy-3-t-butylaminopropoxy) coumarin hydrochloride (CS-359), a new beta-adrenergic blocking agent.

Abstract

β-Adrenergic blocking activity and other pharmacological properties of CS-359, 5-methyl-8-(2-hydroxy-3-t-butylaminopropoxy) coumarin were compared with those of propranolol. CS-359 inhibited the positive chronotropic and the smooth muscle relaxing responses to isoproterenol. The cardiac effect of stellate ganglion stimulation in anesthetized dogs was also abolished. CS-359 given orally to conscious dogs inhibited the positive chronotropic response to isoproterenol given i.v. The β-adrenergic blocking activity of this compound was 2 to 3 times more potent than that of propranolol, both of which were devoid of any intrinsic stimulant activity. Aconitine and ouabain-induced arrhythmias in anesthetized dogs were protected by CS-359. As to local anesthetic action on frog sciatic nerve and guinea-pig cornea, CS-359 had one-tenth the activity of propranolol. Concerning percent reduction of the maximum rate of rise of action potential recorded intracellularly from the ventricular muscle fiber, CS-359 was 3 times less potent than propranolol. It reduced heart rate but had only minor effects on the blood pressure and respiration in anesthetized dogs. These data suggest that CS-359 is a more specific β-adrenergic blocking agent with a greater potency and a less cardiac depression than propranolol.