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Cardiac effects of YM-09538, a new alpha- and beta-adrenoceptor blocking agent, on SA nodal pacemaker activity and contractility in isolated atria and intact dogs.

Abstract
The effects of a newly synthetic alpha- and beta-adrenoceptor blocking agent, YM-09538, on SA nodal pacemaker activity and contractility of atria and intact dogs were studied using isolated and blood-perfused canine atrial muscle preparations supported by a donor dog. Intravenous administration of YM-09538 (10-100 micrograms/Kg) caused hypotension without tachycardia, but was accompanied with bradycardia in anesthetized dogs. In these cases, the SA nodal pacemaker activity and atrial contractility in isolated atria was influenced little. This indicates that the concentration of YM-00538 that induces hypotension has no direct cardiac effects. Direct administration of YM-09538 to isolated atria caused dose-dependent negative chronotropic and inotropic effects, and the potency was 3-30 times less than that of propranolol. In electrically paced preparations, a large dose of YM-09538 produced a uniform depression of the developed tension at all frequencies examined (2-3 Hz). On the other hand, verapamil caused a greater suppression of developed tension at higher frequencies, indicating that the mode of action of YM-09538 is different from that of verapamil.
AuthorsS Chiba, H Watanabe, Y Furukawa, K Iwatsuki
JournalJapanese heart journal (Jpn Heart J) Vol. 23 Issue 4 Pg. 631-6 (Jul 1982) ISSN: 0021-4868 [Print] Japan
PMID6127420 (Publication Type: Journal Article)
Chemical References
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Ethanolamines
  • amosulalol
Topics
  • Adrenergic alpha-Antagonists (pharmacology)
  • Adrenergic beta-Antagonists (pharmacology)
  • Animals
  • Blood Pressure (drug effects)
  • Dogs
  • Ethanolamines (pharmacology)
  • Heart (drug effects)
  • Heart Atria (drug effects)
  • Heart Rate (drug effects)
  • In Vitro Techniques
  • Myocardial Contraction (drug effects)
  • Sinoatrial Node (physiology)

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