Abstract
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.
MeSH terms
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Adrenergic beta-Antagonists / metabolism
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Adrenergic beta-Antagonists / pharmacology*
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Antihypertensive Agents / metabolism
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Antihypertensive Agents / pharmacology
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Binding, Competitive
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Carbazoles / metabolism
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Carbazoles / pharmacology*
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Cardiomyopathy, Dilated / metabolism*
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Carvedilol
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Cyclic AMP / metabolism
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Guanylyl Imidodiphosphate / pharmacology
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Humans
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Iodocyanopindolol
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Metoprolol / metabolism
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Metoprolol / pharmacology
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Myocardium / metabolism*
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Pindolol / analogs & derivatives
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Pindolol / metabolism
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Pindolol / pharmacology
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Propanolamines / metabolism
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Propanolamines / pharmacology*
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Propranolol / metabolism
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Propranolol / pharmacology
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Receptors, Adrenergic, beta / drug effects
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Receptors, Adrenergic, beta / metabolism*
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Vasodilator Agents / metabolism
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Vasodilator Agents / pharmacology*
Substances
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Adrenergic beta-Antagonists
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Antihypertensive Agents
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Carbazoles
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Propanolamines
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Receptors, Adrenergic, beta
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Vasodilator Agents
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Carvedilol
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Guanylyl Imidodiphosphate
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Iodocyanopindolol
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Propranolol
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Pindolol
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Cyclic AMP
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bucindolol
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Metoprolol