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
Hara, Y.; Sato, E.; Miyagishi, A.; Aono, S.; Nakatani, H.
Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 75(7): 707-720
1979
ISSN/ISBN: 0015-5691 PMID: 94296 Document Number: 151736
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.