Adrenoceptor-blocking activity and cardiohemodynamic effects of carvedilol in animals.
The beta-blocking activities of a new beta-adrenoceptor blocking drug, carvedilol, evaluated 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 guinea 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.
Department of Pharmacology, Niigata University School of Medicine, Japan.
T
T
Kawada
T
T
Ishibashi
M
M
Nakazawa
S
S
Satoh
S
S
Imai
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014132:Trachea / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol