[Pharmacological properties of dl-2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-thienyl) thiazole hydrochloride (S-596), a new beta-adrenergic blocking agent (author's transl)]

Abstract

We developed a new beta-adrenergic blocking, antiarrhythmic compound S-596 and compared the findings with those of propranolol or practolol. S-596 antagonized the positive chronotropic and inotropic actions of adrenaline in isolated guinea-pig atria, and blocked the relaxant response to adrenaline of isolated guinea pig tracheal strips. In anesthetized mongrel dogs, S-596 given intravenously inhibited increases in heart rate and myocardial contractile force and decreases in systemic blood pressure induced by isoproterenol. In conscious dogs, the oral administration of S-596 reduced the isoproterenol induced tachycardia and the maximal effect was attained one hour after administration. In this regard S-596 was about 5 times more potent than propranolol, and S-596 was significantly longer-acting than propranolol. Thus, S-596 has greater beta-blocking activity than propranolol. S-596 has a lesser degree of myocardial depressant action than propranolol in spontaneously contracting rat or guinea pig atria and no intrinsic sympathomimetic activity in reserpinized rats. S-596 also has a weaker local anesthetic and antiarrhythmic activity than propranolol, as determined in guinea pigs and rabbits.