[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)].
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.
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002725:Chloroform / Q000031:analogs & derivatives; D004285:Dogs; D004837:Epinephrine; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain; D011217:Practolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D013844:Thiazoles; C024523:arotinolol; D010042:Ouabain; D002725:Chloroform; D011433:Propranolol; D011217:Practolol; D004837:Epinephrine