A Comparison of Beta-Blocking Agents

OF THE MANY beta-receptor blocking agents developed over the past two decades only one, dl-propranolol, has become generally available to American physicians. However, as experience accumulates regarding the safety and efficacy of other beta-blockers, it is likely that at least some of these drugs (many of which are widely used in Europe) will gain approval for use in the United States. Thus an understanding of the comparative properties of these drugs may well prove useful in selecting optimal patient therapy in the future. Nearly all of the beta-blockers used clinically share with isoproterenol, the prototype beta-agonist, an isopropyl substituted amine group thought to produce a high affinity for the beta-receptor.1 They differ from isoproterenol in that each has a different aromatic moiety substituted for the catechol ring, the portion of the catecholamine molecule thought to relate most directly to beta-agonist activity. Thus beta-blockers are all able to combine reversibly with the beta-receptor site and, by a competitive action, exclude substances which might otherwise act as beta-agonists. The net effect of each drug depends not only on receptor site affinity and intensity of competition from beta-agonists, but also on the ability (or inability) of the blocker itself to stimulate the beta-receptor. A spectrum of betaagonist activity exists for the beta-blockers ranging from propranolol, which is essentially devoid of stimulatory activity, 2, 3 to dichloroisoproterenol, which has appreciable agonist properties.3-5 Several drugs-alprenolol,3 6 7 practolol,8 10 and oxprenolol8, 1-occupy an intermediate position in that they have both potent blocking abilities and a weak agonist action. These drugs have been termed "competitive dualists." 12 The physiologic consequences of administering beta-blocking agents depend heavily on the intensity of ambient beta-stimulation. In the presence of high levels of beta-stimulation all effective betablockers act directly to reduce contractility, decrease automaticity in the sinoauricular node and in subsidiary pacemaker tissue, and to reduce conduc-