STUDIES ON dl-4-(2-HYDROXY-3-ISOPROPYLAMINOPROPOXY)-INDOLE (LB 46), A NEW POTENT BETA ADRENERGIC BLOCKING DRUG

¹ Laboratoire de Pharmacologis, Faculté de Médecine, Rue de lÉcole de Médecine, Paris, France

The beta adrenergic blocking effects, the antiarrhythmic properties and the local anesthetic activity of LB 46 have been investigated. In chloralose-anesthetized dogs, LB 46 was 10-to 40-fold more potent than propranolol in antagonizing the cardiovascular effects of isoproterenol and the cardiac stimulating effects of epinephrine, norepinephrine and right stellate ganglion stimulation. In isolated preparations, LB 46 was 3-to 10-fold more potent than propranolol. At beta adrenergic blocking doses, LB 46 was devoid of any intrinsic beta sympathomimetic activity. Furthermore, no modification of the resting cardiovascular parameters of the anesthetized dog could be detected. LB 46 at doses 60-fold higher than the beta adrenergic blocking doses reversed ouabain-induced ventricular tachycardia in dogs, but reversion was then associated with moderate cardiac depressant effects. This reversion occurred although LB 46 had very weak local anesthetic properties. LB 46 appears to be one of the most potent beta adrenergic blocking drugs so far known and one of the least effective in depressing myocardial function.