BETA ADRENERGIC BLOCKING AND CARDIOVASCULAR PROPERTIES OF TWO NEW SUBSTANCES, KÖ1313 AND KÖ 1366

¹ Cardiovascular Pharmacology Section, Wyeth Laboratories, Inc., Radnor, Pennsylvania

The beta adrenergic blocking properties and general cardiovascular actions of two new agents, Kö 1313 and 1366, were examined and compared to effects produced by propranolol. Kö 1313 and 1366 inhibited increases in heart rate and decreases in systemic blood pressure resulting from i.v. administration of isoproterenol in anesthetized dogs. The augmentation of myocardial contractile force due to cardiac sympathetic nerve stimulation was also antagonized as was the relaxant response to isoproterenol on isolated guinea-pig tracheal spirals. The compounds were effective when given p.o. Kö 1313 and 1366 reduced blood pressure but had only minor effects on heart rate and contractile force in anesthetized dogs, whereas propranolol reduced rate and force markedly. After pretreatment with hexamethonium, Kö 1313 and 1366 caused cardiac stimulation. It is concluded that Kö 1313 and 1366 are effective and potent beta adrenergic blocking agents and that they possess a relatively slight intrinsic stimulant component in their profile of activity.