Abstract

The selective beta receptor blocking properties of M&B 17803-A were determined in the anesthetized dog. The effects of isoproterenol on diastolic pressure, heart rate, myocardial contractile force, femoral arterial blood flow and pulmonary airway resistance were determined before and after treatment with M&B 17803-A in a cumulative dose range of 0.03 to 3 mg/kg. M&B 17803-A produced a strong blockade of cardiac beta receptors indicated by a parallel shifting of the isoproterenol dose-response curve. The pA₂ value for the M&B 17803-A-induced inhibition of the positive inotropic response to isoproterenol was 6.88 with a slope of 1.03 and for the inhibition of the positive chronotropic response to isoproterenol was 6.78 with a slope of 1.05. The dose-response curve for the isoproterenol-induced drop in diastolic pressure Was shifted to the right after M&B 17803-A treatment. The pA₂ value for M&B 17803-A on this response was 6.64 with a slope significantly less than 1 (0.71). M&B 17803-A produced no significant blockade of either the increase in femoral blood flow or the decrease in pulmonary airway resistance induced by isoproterenol after the maximum cumulative dose of 3 mg/kg. M&B 17803-A represents an additional prototype of selective beta receptor antagonists producing a strong beta receptor blocking effect in the heart but not in vascular or bronchiolar smooth muscle. The selectivity of the blockade induced by M&B 17803-A differs from that evoked by either practolol or butoxamine as well as propranolol. These results also indicate that the beta receptors subserving cardiac stimulation, vasodilation and bronchodilation are representative of three different beta receptor subtypes in the dog.