Inotropic beta-blocking potency (pA2) and partial agonist activity of propranolol, practolol, sotalol and acebutolol.
The beta-blocking potencies (pA2 values) and cumulative dose responses of the direct effects of dl-propranolol, practolol, acebutolol and sotalol have been characterised in respect of the mechanical performance of isolated cat papillary muscle preparations. pA2 values calculated from antagonism of each of the drugs to the inotropic effect of isoprenaline at 29 degrees C were: dl-propranolol 8.3, practolol 5.6, acebutolol 7.5 and sotalol 4.8. The responses in reserpinized muscles were similar to those in non-reserpinized preparations. dl-Propranolol at concentrations of 10(-5) and 10(-4) M depressed peak developed force (DF) and rate of force development (+dF/dt) by 20% and 60% respectively, with similar but smaller changes in maximum unloaded shortening velocity ('Vmax'). Practolol and sotalol increased DF and +dF/dt by less than 10% at 10(-5) M and by 10-20% at 10(-4) M, with similar but smaller changes in Vmax. Sotalol induced prolonged biphasic contractions at 10(-4) M. Acebutolol had no effect on DF, +dF/dt, or Vmax. Time to peak force and half isometric relaxation time were not altered by any drug. Practolol and acebutolol, generally considered to have partial agonist activity, exerted this to a negligible degree in respect of inotropic effect at less than or equal to 10(-5) M.
D000070:Acebutolol / Q000494:pharmacology; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013015:Sotalol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000070:Acebutolol; D012110:Reserpine; D011433:Propranolol; D013015:Sotalol; D007545:Isoproterenol; D011217:Practolol