Pharmacological profile of carvedilol, a compound with beta-blocking and vasodilating properties.
We found compounds in the class of "phenoxyethylamines" that in addition to a beta-blocking activity also showed vasodilatation. Using screening investigations in rabbits, substances were sought that possess both properties in the same dose or concentration range. These conditions were fulfilled, for example, by carvedilol. In further, more detailed, pharmacological investigations it was found that the substances are also active after oral administration. The cause of the hypotensive action of carvedilol is a fall in total peripheral vascular resistance resulting from a direct vasodilating action. This direct vasodilating action is demonstrable in aortic strips independently of whether the preparation has been previously contracted with noradrenaline, potassium chloride, or a thromboxane agonist. Carvedilol behaves in this respect more like glyceryl trinitrate and less like the alpha 1-blocker prazosin. Because of the additional beta-blocking action, there is only a slight activation of reflex mechanisms even at clearly hypotensive doses in comparison with equipotent doses of other vasodilators (dihydralazine and nicardipine). With respect to its beta-blocking action, carvedilol is very similar to propranolol. It does not have any intrinsic sympathomimetic activity or any cardioselectivity, and its membrane-stabilizing property is approximately the same as that of propranolol. The balanced ratio of the vasodilatation and beta-blocking actions makes this substance an interesting choice for the treatment of various cardiovascular diseases.
Strein
K
K
Department of Experimental Cardiovascular Research, Boehringer Mannheim GmbH, F.R.G.
Sponer
G
G
Müller-Beckmann
B
B
Bartsch
W
W
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009126:Muscle Relaxation; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D014665:Vasodilator Agents / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D012083:Renin