INTRINSIC SYMPATHOMIMETIC ACTIVITY OF PENBUTOLOL

Six healthy volunteers took part in a randomized, single-blind, crossover study to quantitate the intrinsic sympathomimetic activity (ISA) of penbutolol in comparison with one drug possessing ISA (alprenolol) and with the standard non-ISA drug (propranolol). Single intravenous and one week oral administrations were studied. Complete parasympathetic and sympathetic isolation of the heart was obtained by administration of atropine 0.04 mg/kg body weight i. v. and propranolol 0.4 mg/kg i. v., or corresponding equipotent doses of alprenolol 0.4 mg/kg i. v. and penbutolol i. v. 0.08 mg/kg. In the chronic, oral study propranolol 160 mg b. i. d. was given, or corresponding equipotent doses of alprenolol (400 mg b. i. d.) or penbutolol (40 mg b. i. d.). The test procedure included measurement of heart rate and blood pressure in the supine, sitting and standing positions, and during isometric and dynamic exercise. ISA was calculated by comparison of the change in of heart rate with that produced by propranolol. The ISA of alprenolol was 22-26% and of penbutolol 12-18% of maximal sympathetic activity. Isometric and dynamic exercise gave comparable ISA values. © 1979 Springer-Verlag.