Abstract:
:Bucindolol is a nonselective beta-adrenergic receptor antagonist that has additional vasodilating properties. Because some beta-adrenergic receptor antagonists such as cyanopindolol are used as 5-HT1A/5-HT1B receptor antagonists, we tested the hypothesis that bucindolol can interact with 5-HT receptors. Both in vitro and in vivo methods were used to examine the interaction of bucindolol with 5-HT receptors relevant to the cardiovascular system-the 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2B receptors-and with alpha1-adrenergic receptors. In binding studies, bucindolol displayed high affinity for the 5-HT1A receptor (Ki, 11 nM), modest affinity for the 5-HT2A receptor (Ki, 382 nM), and no measurable affinity for the 5-HT1D receptor; binding affinity for the 5-HT2B receptor was not studied. Bucindolol also displayed significant binding affinity (Ki, 69 nM) for the alpha1-adrenergic receptors. Alpha1-Adrenergic receptor antagonist activity was confirmed by the ability of bucindolol (1 mg/kg) to act as a competitive antagonist against 0.01-30 microg/kg phenylephrine-induced pressor responses in conscious rats. In conscious permanently instrumented rats, bucindolol (0.1-3.0 mg/kg, i.v.) did not cause bradycardia similar to that elicited by the 5-HT1A-receptor agonist 8-OH-DPAT (3-300 microg/kg, i.v.), nor did bucindolol (1 mg/kg) block the 8-OH-DPAT-induced bradycardia. Bucindolol (10(-9)-10(-5) M) did not cause relaxation in the PGF2alpha-contracted, endothelium-intact porcine coronary artery, nor did bucindolol (10(-5) M) block 5-HT-induced coronary artery relaxation, indicating that bucindolol does not have significant interactions at the 5-HT1D receptor. Bucindolol also displayed no agonist activity at the 5-HT2A and 5-HT2B receptor (endothelium-denuded rat thoracic aorta and rat stomach fundus, respectively), but did act as a weak 5-HT2A-receptor antagonist (-log K(B) [M] = 5.4+/-0.1) and 5-HT2B-receptor antagonist (-log K(B) [M] = 7.8+/-0.1). Thus, these data suggest that bucindolol lacks the ability to activate the 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2B receptor, but can block alpha1-adrenergic receptors and act as a weak 5-HT2A- and 5-HT2B-receptor antagonist. The relevance of these serotoninergic effects as it pertains to the mechanism of bucindolol-induced vasodilation is unknown.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Watts SW,Fink GD,Silver PJ,Cushing DJdoi
10.1097/00005344-200001000-00004subject
Has Abstractpub_date
2000-01-01 00:00:00pages
29-36issue
1eissn
0160-2446issn
1533-4023journal_volume
35pub_type
杂志文章abstract::To evaluate the role of angiotensin II (AII) on diastolic function during post-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental animals were maintained on either irbesartan, a selective AT1-receptor antagonist, or no treatmen...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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abstract::The usual drugs for migraine attacks carry risks of increased frequency, resistance to other treatment, drug dependency, and abuse. Ergotamines may also be vascular risk factors. Alternative drugs without these risks would be useful. Flunarizine could be an alternative. Migraine cannot be reduced to molecular pathophy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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更新日期:1991-01-01 00:00:00
abstract::From the membrane fraction of cultured human renal adenocarcinoma (ACHN) cells, two endothelin-2-converting enzymes (ECE-2A and ECE-2B) were solubilized with detergent Lubrol PX and separated by hydrophobic butyl fast-performance liquid chromatography. The pH range of the converting activity of ECE-2B for big endothel...
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:2004-06-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1992-05-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1994-02-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg...
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journal_title:Journal of cardiovascular pharmacology
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