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Pharmacological effects of an aldehyde type alpha/beta-adrenoceptor blocking agent with vasodilating properties.

Abstract
KMUP 880723 (0.5, 1.0, and 3.0 mg/kg, iv) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880723 (1.0 mg/kg, iv) also markedly inhibited both the tachycardia effects induced by (-)isoproterenol and arterial pressor responses induced by phenylephrine. In the isolated Wistar rat right atria, left atria, and guinea pig tracheal strips, KMUP 880723 competitively antagonized the (-)isoproterenol-induced positive chronotropic effects, inotropic effects, and tracheal relaxation effects in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that KMUP 880723 was a beta(1)/beta(2)-adrenoceptor competitive antagonist. The apparent pA(2) values were 6.89+/-0.10 in the right atria, 7.02+/-0.09 in the left atria, and 6.59+/-0.11 in the trachea, indicating that KMUP 880723 was a nonselective beta-adrenoceptor blocker. In thoracic aorta experiments, KMUP 880723 also produced a competitive antagonism of norepinephrine-induced contraction with a pA(2) value of 7.14+/-0.06. In isolated rat thoracic aorta, KMUP 880723 more potently relaxed the contractions induced by norepinephrine (3 x 10(-6) M) than those by high K(+) (75 mM). In the radioligand-binding assay, the pK(i) values of [3H]CGP-12177 binding to rat ventricle and lung membranes were 6.56 and 6.40, respectively, and the value of [3H]prazosin binding to rat brain membranes was 6.66. These results further confirmed the alpha/beta-adrenoceptor blocking activities of KMUP 880723 reported in the functional studies. We conclude that KMUP 880723 is a nonselective beta-adrenoceptor antagonist with alpha-adrenoceptor blocking-associated vasorelaxant activity.
AuthorsC C Chiu, Y T Lin, C H Tsai, J C Liang, L C Chiang, J R Wu, I J Chen, J L Yeh
JournalGeneral pharmacology (Gen Pharmacol) Vol. 34 Issue 6 Pg. 391-400 (Jun 2000) ISSN: 0306-3623 [Print] England
PMID11483288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Benzaldehydes
  • Cardiovascular Agents
  • N-(4-(2-hydroxy-3-(2-methoxy-1-oxyethylaminobenzene)propoxy))benzaldehyde
  • Vasodilator Agents
  • Atenolol
  • Mecamylamine
  • Propranolol
  • Isoproterenol
  • Labetalol
Topics
  • Adrenergic alpha-Antagonists (analysis, pharmacology)
  • Adrenergic beta-Antagonists (analysis, pharmacology)
  • Animals
  • Aorta (drug effects)
  • Atenolol (analysis, pharmacology)
  • Benzaldehydes (pharmacology)
  • Blood Pressure (drug effects)
  • Cardiovascular Agents (pharmacology)
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart Atria (drug effects)
  • Heart Rate (drug effects)
  • Isoproterenol (analysis, pharmacology)
  • Labetalol (analysis, pharmacology)
  • Mecamylamine (analysis, pharmacology)
  • Models, Animal
  • Muscle, Smooth, Vascular (drug effects)
  • Myocardial Contraction (drug effects)
  • Propranolol (analysis, pharmacology)
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Regression Analysis
  • Stimulation, Chemical
  • Vasodilator Agents (pharmacology)

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