Cardiospecificity of -receptor blockade. A comparison of the relative potencies on cardiac and peripheral vascular -adrenoceptors of propranolol, of practolol and its ortho-substituted isomer, and of oxprenolol and its para-substituted isomer.
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An attempt has been made to compare quantitatively the relative potencies of various compounds in blocking the effects of isoprenaline on peripheral blood flow and on heart rate. In anaesthetized dogs a cuff flow probe was placed around the descending aorta, and the inferior mesenteric artery was cannulated in a retrograde direction. Two to three-fold increases in peripheral blood flow conductance were produced by intra-arterial injections of isoprenaline so small that they had little effect on heart rate. Effects of larger intravenous doses of isoprenaline on heart rate were then measured, so that dose response curves for the peripheral and cardiac effects of isoprenaline were obtained in the same dog. Practolol blocked peripheral β-receptors to some extent, but was eight times more potent on the heart. Transference of the acetamide substituent from the para to the ortho position on the ring led to a loss of cardiospecificity. Conversely, the para-substituted isomer of oxprenolol was totally cardiospecific. It had the same potency as oxprenolol on the heart, but did not block the effects of isoprenaline on blood flow at all. Oxprenolol itself, and propranolol, were more potent in blocking peripheral than cardiac β-receptors.