Receptor pharmacology of carvedilol in the human heart.
The beta-blocker and vasodilator carvedilol was examined in preparations of human ventricular myocardium. Carvedilol is a high-affinity, slightly beta 1-selective competitive beta-blocking agent, with a KD for beta 1-receptors of approximately 4-5 nM and a selectivity of sixfold to 39-fold for beta 1-receptors rather than beta 2-receptors, depending on the method used to assess subtype potency. Carvedilol also is a potent alpha 1-blocking agent, with a beta 1: alpha 1-blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2-receptors and human myocardial membranes containing both beta 1- and beta 2-receptors, carvedilol exhibited the unique property of guanine nucleotide-modulatable binding. This is a property shared with bucindolol, another beta-blocker and vasodilator that is structurally similar to carvedilol. Despite the presence of guanine nucleotide-modulatable binding, no intrinsic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes.
Bristow
M R
MR
Cardiology Division, University of Utah Medical Center, Salt Lake City.
Larrabee
P
P
Minobe
W
W
Roden
R
R
Skerl
L
L
Klein
J
J
Handwerger
D
D
Port
J D
JD
Müller-Beckmann
B
B
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002227:Carbazoles / Q000378:metabolism / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D000077261:Carvedilol; D000242:Cyclic AMP / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D020120:Iodocyanopindolol; D008790:Metoprolol / Q000378:metabolism / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D000077261:Carvedilol; D006165:Guanylyl Imidodiphosphate; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D000242:Cyclic AMP; C024307:bucindolol; D008790:Metoprolol