Adrenoceptor-Blocking Activity and Cardiohemodynamic Effects of Carvedilol in Animals

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Abstract
The .beta.-blocking activities of a new .beta.-adrenoceptor blocking drug, carvediol, evaluted in isolated atria and trachea of the guinea pig were 2.0 (.beta.1) and 3.2 times (.beta.2), respectively, as potent as those of propranolol. Carvedilol exhibited the .alpha.-blocking activities in the aorta of guniea pigs and rats. Carvedilol was 2 and 50 times less potent in guinea pigs and rats, respectively, than prazosin as an .alpha.-blocker. Thus, the .alpha.-blocking activities were twice as potent as the .beta.-blocking activity in the rat and one-fifth that of the .beta.-blocking activity in the guinea pig. In anesthetized open-chest dogs, the .beta.-blocking activity of carvedilol was 1.5 times more potent than that of propranolol and had 3.8 times the .alpha.-blocking activity. Thus, carvedilol is a nonselective .beta.-blocking drug with a potent .alpha.-blocking activity. Carvedilol and propranolol showed dose-dependent and significant decreases in the blood pressure, total cardiac output, left ventricular pressure, dp/dt, heart rate, coronary flow, and oxygen consumption in anesthetized open-chest dogs. Carvedilol decreased the total peripheral resistance significantly (the decrease was not proportional to the decreases in the blood pressure at high doses), while propranolol increased it significantly and dose-dependently. These results indicate the importance of .alpha.-adrenoceptor blocking activity in the decrease in blood pressure produced by carvedilol.